Serum Hepatocyte Growth Factor Research Articles

Potential of dehydroepiandrosterone and quercetin to ameliorate copper oxide nanoparticles induced hepatotoxicity in albino wistar rats.

The current investigation was designed as an experimental endeavor to explore the protective efficacy of dehydroepiandrosterone (DHEA) and quercetin against hepatotoxicity induced by copper oxide (CuO) nanoparticles. Rats were subjected to CuO nanoparticle intoxication through intraperitoneal injection of 150mg/kg b.w. for three weeks, followed by the administration of the aforementioned antioxidants for an additional three weeks. This study systematically tracked alterations in liver enzymatic activity, antioxidant levels, apoptotic markers, and histopathological changes using the comet assay. CuO nanoparticle-intoxicated rats exhibited a significant increase in serum alanine transaminase aspartate aminotransferase (AST), and bilirubin levels, coupled with a noteworthy reduction in serum albumin. Moreover, there was a marked rise in serum tumor necrosis factor-alpha levels, concomitant with a significant decline in serum hepatocyte growth factor (HGF). Caspase-3 and Bax mRNA levels in the serum showed a substantial increase, while serum Bcl-2 mRNA levels witnessed a significant decrease. Liver tissue levels of malondialdehyde (MDA) and nitric oxide (NOx) experienced a significant elevation, and DNA damage was observed through the comet assay. Histopathological examination of the liver tissue substantiated these aforementioned findings. Administration of the antioxidants DHEA or quercetin, either individually or in combination, mitigated the parameters of hepatotoxicity to varying extents. In summary, the hepatic genotoxicity induced by CuO nanoparticles demonstrated improvement following the administration of either DHEA or quercetin. Additionally, their combined administration exhibited a more potent protective potential.

Prognostic Role of Serum Vascular Endothelial Growth Factor and Hepatocyte Growth Factor Post Stereotactic Body Radiation in Advanced Hepatocellular Carcinoma

Prognostic Role of Serum Vascular Endothelial Growth Factor and Hepatocyte Growth Factor Post Stereotactic Body Radiation in Advanced Hepatocellular Carcinoma

Serum Hepatocyte Growth Factor Concentration Correlates with Albuminuria in Individuals with Optimal Blood Pressure and Untreated Arterial Hypertension.

Background/Objectives: Hepatocyte growth factor (HGF) is a protective factor against acute renal injury and chronic renal fibrosis. A positive correlation between HGF and blood pressure (BP) has been established. This study aimed to determine the association between serum HGF concentration and albuminuria in subjects with optimal blood pressure (OBP) and untreated arterial hypertension (UAH), as well as its association with BP levels, serum glucose levels, and inflammatory markers. Methods: Data from 563 subjects were analyzed. Albuminuria was normalized to urine creatinine and expressed as the albumin/creatinine ratio (ACR). HGF, serum glucose, C-reactive protein, and blood leucocyte counts were measured. BP was measured and subjects were divided into optimal blood pressure (BP < 120/80 mmHg, N = 295) and untreated arterial hypertension (BP > 140/90 mmHg, N = 268) groups. Results: The subjects with UAH were significantly older and had higher values of body mass index, waist circumference, serum total and LDL cholesterol levels, triglyceride levels, fasting glucose levels, and ACR (all p < 0.001). A significant positive correlation was found between serum HGF concentration and ACR in both groups. There was no difference or correlation between HGF and BP or inflammatory markers in either group. The multivariate regression analysis identified serum HGF concentration as a strong predictor of ACR increase (Beta = 0.376, p < 0.001). Conclusion: This study found that serum HGF concentration is associated with albuminuria not only in individuals with untreated arterial hypertension, but also in those with optimal blood pressure. The results suggest that serum HGF is an independent predictor of ACR increase in both groups.

Nutritional supplementation of breeding hens may promote embryonic development through the growth hormone-insulin like growth factor axis

The late stage of embryo development is a crucial period of metabolic changes, with rapid organ development requiring a substantial supply of nutrients. During this phase, maternal nutritional levels play a vital role in the growth, development, and metabolism of the offspring. In this study, we added 2 doses of β-carotene (βc) (120 mg/kg and 240 mg/kg) to the daily diet of Hailan Brown laying hens to investigate the impact of maternal nutritional enrichment on embryo development. Maternal nutrition supplementation significantly increased the expression of chicken embryo liver index, growth hormone (GH), insulin-like growth factor-1 (IGF-1), and hepatocyte growth factor (HGF) in serum. At the same time, the expression of GH/growth hormone receptor (GHR), IGF-1 mRNA, and Proliferating Cell Nuclear Antigen (PCNA) protein in the liver was upregulated, indicating that maternal nutrition intervention may promote chicken embryo liver development through the GH-IGF-1 axis. Transcriptome sequencing results showed that differential genes in liver after maternal nutritional supplementation with β-carotene were enriched in pathways related to cell proliferation and metabolism. Consequently, we postulated that maternal β-carotene supplementation might operate via the GH-IGF-1 axis to regulate the expression of genes involved in growth and development, thereby promoting liver development. These results contribute to formulating more effective poultry feeding strategies to promote offspring growth and development.

Gender effect of glucose, insulin/glucagon ratio, lipids, and nitrogen-metabolites on serum HGF and EGF levels in patients with diabetes type 2.

Hepatocyte growth factor (HGF) exhibits potent growth-inducing properties across various tissues, while epidermal growth factor (EGF) acts as a molecular integration point for diverse stimuli. HGF plays a crucial role in hepatic metabolism, tissue repair, and offers protective effects on epithelial and non-epithelial organs, in addition to its involvement in reducing apoptosis and inflammation, underscoring its anti-inflammatory capabilities. The HGF-Met system is instrumental in hepatic metabolism and enhancing insulin sensitivity in animal diabetes models. Similarly, the EGF and its receptor tyrosine kinase family (EGFR) are critical in regulating cell growth, proliferation, migration, and differentiation in both healthy and diseased states, with EGF also contributing to insulin sensitivity. In this observational study, we aimed to identify correlations between serum levels of HGF and EGF, insulin, glucagon, glucose, and primary serum lipids in patients with type 2 diabetes mellitus (DM), taking into account the impact of gender. We noted differences in the management of glucose, insulin, and glucagon between healthy men and women, potentially due to the distinct influences of sexual hormones on the development of type 2 DM. Additionally, metabolites such as glucose, albumin, direct bilirubin, nitrites, and ammonia might influence serum levels of growth factors and hormones. In summary, our results highlight the regulatory role of insulin and glucagon in serum glucose and lipids, along with variations in HGF and EGF levels, which are affected by gender. This link is especially significant in DM, where impaired cell proliferation or repair mechanisms lead to metabolic changes. The gender-based differences in growth factors point to their involvement in the pathophysiology of the disease.

Postoperative Intimal Hyperplasia: Review from My Research.

Postoperative intimal hyperplasia is the major cause of the vein graft occlusion. It is very important to establish an animal model for the start of research. After my vascular surgery residency in Japan, I started my research work on postoperative intimal hyperplasia at the University of Wisconsin-Madison. My research showed that endothelial injury and monocyte infiltration is the key for postoperative intimal hyperplasia, which is very similar to Ross' pathogenesis of atherosclerosis as an inflammatory disease. Focusing on postoperative intimal hyperplasia as an inflammatory disease, especially on tumor necrosis factor-α, FR-167653 (tumor necrosis factor-α suppressive agent, inhibitor of p 38 mitogen-activated protein kinase; Fujisawa Pharmaceutical Co., Ltd., Japan) is found to suppress postoperative intimal hyperplasia in a rat model by reducing serum monocyte chemoattractant protein-1 levels. However, FR-167653 is not commercially available today. Because endothelial injury is the first step of postoperative intimal hyperplasia, I investigated whether the free radical scavenger, edaravone (Radicut, Mitsubishi Tanabe Pharma Co., Japan), which alleviates the endothelial injury in vitro , can also suppress postoperative intimal hyperplasia. Moreover, the free radical scavenger edaravone (Radicut®, Mitsubishi Tanabe Pharma Co.) is also found to suppress postoperative intimal hyperplasia, by alleviating endothelial injury. In clinical settings, it is very important to detect postoperative intimal hyperplasia before its establishment. Hepatocyte growth factor is not only a hepatic growth factor but also a vascular endothelial growth factor. Recently, serum hepatocyte growth factor level was found to be a candidate biomarker for postoperative intimal hyperplasia in our rat model.

The protective effects of Nigella sativa, thymoquinone and bentonite in experimental aflatoxicosis model in broilers

The aim of this study was to determine the preventive efficacy of black seed (Nigella sativa L.), thymoquinone and Na bentonite on biomarkers of tissue degeneration in the liver and other organs induced by aflatoxin (AF) in broilers. One hundred broiler chicks were divided into 10 equal groups and fed for 28 days. The animals received feed with 2 mg/kg total aflatoxin, Nigella sativa (NS; 5%), thymoquinone (TMQ; 300 mg/kg) and Na bentonite (BNT; 10 g/kg) both individually and in combination. At the end of the experiment, blood and liver tissue samples were collected. AF treatment significantly increased serum and liver 8-hydroxy-2’-deoxyguanosine(8-OHdG), serum transforming growth factor β (TGF-β), and liver total antioxidant capacity (TAC) levels, whereas it significantly decreased liver TGF-β and serum TAC levels compared to the control. However, there were no changes in the serum and liver hepatocyte growth factor (HGF) levels from AF. Both individual and combined addition of NS, BNT and TMQ to AF-contaminated feed significantly improved liver 8-OHdG, liver TAC and serum TGF-β levels. Serum 8-OHdG levels were ameliorated only in the AF+BNT+TMQ group. In addition, the AF+BNT+NS and AF+BNT+TMQ groups showed significant improvement in liver 8-OHdG, liver TGF-β and liver TAC levels. We conclude that NS and TMQ supplementation to AF-contaminated feed may be beneficial against aflatoxicosis in broilers.

Glycoprotein non-metastatic melanoma protein B expression correlates with the prognosis of acute liver injury/failure.

Background: Glycoprotein non-metastatic melanoma protein B (GPNMB) is expressed in macrophages during recovery from acute liver injury (ALI) in carbon tetrachloride (CCl4)-induced liver injury model mice. In this retrospective study, we assessed whether GPNMB levels in the serum and injured liver correlate with liver injury severity and prognosis in patients with ALI or acute liver failure (ALF). Methods: The study involved 56 patients with ALI or ALF who visited the Kagoshima University Hospital. Serum GPNMB level was measured over time, and the localization, proportion, origin, and phenotype of GPNMB-expressing cells in the injured liver were assessed. Finally, the phenotypes of human monocyte-derived macrophages and peripheral blood mononuclear cells (PBMCs) of patients with ALI and ALF were analyzed. Results: Peak GPNMB levels were significantly higher in patients with ALF and hepatic encephalopathy (HE), as well as in those who underwent liver transplantation or died, than in others. The peak GPNMB level correlated with prothrombin activity, prothrombin time-international normalized ratio, Model for End-stage Liver Disease score, and serum hepatocyte growth factor level. GPNMB was expressed in CD68-positive macrophages, and its level increased with the severity of liver injury. The macrophages showed the same polarization as M2c macrophages induced with interleukin-10 from human monocytes. Moreover, PBMCs from patients with ALF exhibited an immunosuppressive phenotype. Conclusion: We found that GPNMB levels in the serum and injured liver, which increased in patients with ALF, especially in those with HE, correlated with the severity of liver injury and prognosis of ALI and ALF. Moreover, GPNMB-positive macrophages exhibited the M2c phenotype. Our results indicate that persistently high GPNMB levels may be a prognostic marker in patients with ALI and ALF.

Correlation between Hepatocyte Growth Factor (HGF) with D-Dimer and Interleukin-6 as Prognostic Markers of Coagulation and Inflammation in Long COVID-19 Survivors.

In general, an individual who experiences the symptoms of Severe Acute Respiratory Syndrome Coronavirus 2 or SARS-CoV-2 infection is declared as recovered after 2 weeks. However, approximately 10-20% of these survivors have been reported to encounter long-term health problems, defined as 'long COVID-19', e.g., blood coagulation which leads to stroke with an estimated incidence of 3%, and pulmonary embolism with 5% incidence. At the time of infection, the immune response produces pro-inflammatory cytokines that stimulate stromal cells to produce pro-hepatocyte growth factor (pro-HGF) and eventually is activated into hepatocyte growth factor (HGF), which helps the coagulation process in endothelial and epithelial cells. HGF is a marker that appears as an inflammatory response that leads to coagulation. Currently, there is no information on the effect of SARS-CoV-2 infection on serum HGF concentrations as a marker of the prognosis of coagulation in long COVID-19 survivors. This review discusses the pathophysiology between COVID-19 and HGF, IL-6, and D-dimer.

Association of Serum Hepatocyte Growth Factor Level with Systemic Inflammatory Biomarkers in Patients with Pancreatobiliary Cancer.

Hepatocyte growth factor is a cytokine secreted by the stromal cells in the tumor microenvironment. There is little information about the clinical significance of serum hepatocyte growth factor level in patients diagnosed with pancreatobiliary cancer. The objective of the current study was to investigate the relationship between serum hepatocyte growth factor level with inflammation markers and the clinical features of patients with pancreatobiliary cancer. A total of 62 patients with pancreatobiliary cancer were included in this study. Serum hepatocyte growth factor concentrations were evaluated utilizing the enzyme-linked immunosorbent assay method. The median serum hepatocyte growth factor level was 329.1 ng/mL (1.4-1051.1). The patients were categorized into 2 groups as those below the median hepatocyte growth factor level (low hepatocyte growth factor) and those above the median hepatocyte growth factor level (high hepatocyte growth factor). While 40.9% of the patients without metastasis were observed to be in the high hepatocyte growth factor group, 72.2% of the metastatic patients were observed to be in the high hepatocyte growth factor group (P = .025). The median levels of monocyte, monocyte-to-lymphocyte ratio, C-reactive protein, and C-reactive protein-to-albumin ratio were found to be significantly higher in the high hepatocyte growth factor group as compared to the low hepatocyte growth factor group (P < .050). The significant relationship between serum hepatocyte growth factor level and systemic inflammation markers in patients with pancreatobiliary cancer is shown for the first time in our study. This study, which showed a significant relationship between the presence of metastasis and serum hepatocyte growth factor level, suggests that serum hepatocyte growth factor level may be a prognostic biomarker in patients who are diagnosed with pancreatobiliary cancer.

Improvement of physical activity significantly reduced serum hepatocyte growth factor levels in a general population: 10year prospective study.

Hepatocyte growth factor (HGF) is an adipocytokineelevated in obese subjects. We have previously reported that serum HGF levels were significantly associated with insulin resistance or components of the metabolic syndrome. However, it has been unknown how physical activity (PA) affects HGF levels after a long-term follow-up. Our aim was to clarify the association between PA changes and HGF levels as well as cerebro-cardiovascular disease (CVD) development, during a 10year follow-up period in a Japanese general population. Of 1320 subjects who received a health check-up examination in Tanushimaru town in 1999, 903 subjects (341 males and 562 females), who received the examination both in 1999 and 2009 were enrolled. We evaluated their PA levels by Baecke questionnaire in 1999 and by a simple questionnaire in 2009. We measured the HGF levels by ELISA method in 1999 and 2009. We divided the subjects into four PA groups, stable low PA, increased PA, decreased PA, and stable high PA. Using these questionnaires, we compared their PA and HGF levels after an interval of 10years. A significant inverse association was found between PA changes and HGF levels at 10years, after adjustment for age and sex. The HGF levels of the increased PA group were significantly lower than stable low PA (p = 0.038), and the increased PA group showed reduced CVD development compared to the stable low PA group after adjustment for age and sex (p = 0.012). Our data demonstrated that improvement of PA levels was associated with reduced HGF levels and CVD development.

Donor and Recipient Adipose-Derived Mesenchymal Stem Cell Therapy for Rat Lung Transplantation

Mesenchymal stem cells (MSCs) are beginning to be proven as immunosuppressant in the field of organ transplantation. However, the effects of MSC origin (donor or recipient) on immunosuppression are not clear. Hence, we investigated the effects of recipient and donor adipose-derived MSCs (ADMSCs) on immunosuppression in a rat lung transplantation model. Subjects were divided into no treatment, tacrolimus administration, recipient ADMSC administration, donor ADMSC administration, and mixed donor and recipient ADMSC administration groups. ADMSC-administered groups were also treated with tacrolimus. Histologic study, immunofluorescence, immunohistochemistry, enzyme-linked immunosorbent assay, and polymerase chain reaction were used for various analyses. Fluorescently labeled ADMSCs were predominant in the grafted donor lung, but not in the recipient lung, on day 5. On day 7, the pathologic rejection grades of the grafted donor lung were significantly lower in the ADMSC-administered groups (P < .05) and did not differ among these groups. Although serum hepatocyte growth factor and vascular endothelial growth factor levels did not differ among the groups, interleukin 10 level was slightly higher in the ADMSC-administered groups. The numbers of infiltrating regulatory T cells in the grafted lung were significantly higher in the ADMSC-administered groups (P < .05) but did not differ with cell origin. Transcriptional analysis suggested interleukin 6 suppression to be the main overlapping immunosuppressive mechanism, regardless of origin. Therefore, a donor or recipient origin may not influence the immunosuppressive efficacy of ADMSCs in our rat lung transplantation model. Collectively, the results indicate that allogenic ADMSCs, regardless of their origin, may exert similar immunosuppressive effects in clinical organ transplantation.

Effect of hepatocyte growth factor on mice with hypoxic pulmonary arterial hypertension: a preliminary study.

To study the association between hepatocyte growth factor (HGF) and treatment response in mice with hypoxic pulmonary arterial hypertension (HPAH) and the possibility of HGF as a new targeted drug for HPAH. After successful modeling, the HPAH model mice were randomly divided into two groups: HPAH group and HGF treatment group (tail vein injection of recombinant mouse HGF 1 mg/kg), with 10 mice in each group. Ten normal mice were used as the control group. After 5 weeks, echocardiography was used to measure tricuspid peak velocity, right ventricular systolic pressure, right ventricular hypertrophy index, and right ventricular/body weight ratio; the Griess method was used to measure the content of nitric oxide in serum; ELISA was used to measure the serum level of endothelin-1; transmission electron microscopy was used to observe changes in the ultrastructure of pulmonary artery. Compared with the HGF treatment and normal control groups, the HPAH group had significantly higher tricuspid peak velocity, right ventricular systolic pressure, right ventricular hypertrophy index, and right ventricular/body weight ratio (P<0.05). The transmission electron microscopy showed that the HPAH group had massive destruction of vascular endothelial cells and disordered arrangement of the elastic membrane of arteriolar intima with rupture and loss. The structure of vascular endothelial cells was almost complete and the structure of arterial intima elastic membrane was almost normal in the HGF treatment group. Compared with the normal control and HGF treatment groups, the HPAH group had significantly higher serum levels of nitric oxide and endothelin-1 (P<0.05). Increasing serum HGF level can alleviate the impact of HPAH on the cardiovascular system of mice, possibly by repairing endothelial cell injury, improving vascular remodeling, and restoring the normal vasomotor function of pulmonary vessels.

Abstract 5138: Cetuximab resistance induced by hepatocyte growth factor is overcome by MET inhibition in KRAS, NRAS, and BRAF wild-type colorectal cancer

Abstract Background: Recent evidence has highlighted the role of hepatocyte growth factor (HGF) as a putative biomarker to predict EGFR inhibitor resistance. This study investigated the impact of plasma HGF levels on EGFR inhibition and the therapeutic implications of MET inhibition in KRAS, NRAS, and BRAF (RAS/RAF) wild-type colorectal cancer (CRC). Methods: Clinical outcomes were analyzed according to the plasma HGF levels in patients with metastatic CRC (mCRC) receiving palliative first-line cetuximab or bevacizumab + FOLFIRI chemotherapy. Then, in vitro experiments were conducted to validate the clinical findings and to establish pre-clinical evidence of MET inhibition in the HGF-high population. Results: From March 2015 to September 2019, a total of 80 patients were enrolled. The median age was 63 (range, 24-85) years. Of these, 45 patients (56.2%) were treated with bevacizumab + FOLFIRI and 35 patients (43.8%) were treated with cetuximab + FOLFIRI. Among patients with evaluable disease (43 patients (95.6%) in the bevacizumab group and 34 patients (97.1%) in the cetuximab group), the objective response rate was 60.0% and 37.8%, respectively (p=0.162). The median serum HGF level was 374.75 (range, 9.43-30,644.44) pg/mL, and the optimal cut-off value of HGF levels was 12.70 pg/mL by the maximal chi-square method. During a median follow-up of 29.3 (range, 1.2-71.3) months, both progression-free survival (PFS) and overall survival (OS) were significantly shorter in the high HGF group compared with the low HGF group: median 11.8 (95% confidence interval [CI], 10.5-13.1) months vs. 24.7 (95% CI, 23.4-25.9) months for PFS (p=0.009), and median 21.1 (95% CI, 17.9-24.3) months vs. not reached for OS (p=0.018). The difference in PFS and OS was statistically significant in the cetuximab group (p=0.003 for PFS and p=0.035 for OS), but not in the bevacizumab group. In five RAS/RAF wild-type CRC cell lines (Caco-2, COLO 320DM, KM12C, SNU-C1, and SNU-C4), the addition of HGF activated ERK1/2 and AKT via MET phosphorylation. In the cytotoxicity assays, Caco-2 and SNU-C4 were relatively sensitive to cetuximab compared with the others and, in the presence of HGF, cetuximab sensitivity was significantly decreased in the two cells. Moreover, capmatinib, a MET inhibitor, abrogated the effect of HGF on common downstream signaling pathways of EGFR and MET and thus the cetuximab resistance was significantly overcome in vitro. Conclusions: Among patients with mCRC receiving cetuximab + FOLFIRI, those with high plasma HGF levels had significantly worse PFS and OS. HGF induced cetuximab resistance by AKT and ERK activation while capmatinib, a MET inhibitor, significantly increased the anti-tumor effects of cetuximab in the presence of HGF in vitro. Our data may provide evidence of future clinical trials of dual EGFR and MET targeting strategies in patients with HGF-high, RAS/RAF wild-type mCRC. Citation Format: Sang-A Kim, Hyejoo Park, Kui-Jin Kim, Ji-Won Kim, Ji Hea Sung, Milang Nam, Ju Hyun Lee, Eun Hee Jung, Koung Jin Suh, Ji Yun Lee, Se Hyun Kim, Jeong-Ok Lee, Jin Won Kim, Yu Jung Kim, Jee Hyun Kim, Soo-Mee Bang, Jong Seok Lee, Keun-Wook Lee. Cetuximab resistance induced by hepatocyte growth factor is overcome by MET inhibition in KRAS, NRAS, and BRAF wild-type colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5138.

SERUM HEPATOCYTE GROWTH FACTOR CONCENTRATION IS ASSOCIATED WITH BLOOD PRESSURE IN SUBJECTS WITH PREHYPERTENSION

Objective: Hepatocyte growth factor (HGF) is a pleiotropic factor that regulates cellular processes such as cell survival, proliferation, migration, and differentiation. Serum HGF concentration is associated with systolic blood pressure (BP) and is higher in hypertensive than in normotensive individuals, especially if complications of arterial hypertension are developed. Our aim was to determine the association of serum HGF concentration in subjects with prehypertension. Design and method: Data from 612 subjects (57,8% women, average age 41 years) was nalysed. After clinical examination, fasting blood and urine samples were drawn. HGF was measured using a commercial test. BP was measured according to the ESC/ESH guidelines. Based on BP values, subjects were divided into two groups: OBP - subjects with optimal blood pressure (BP &lt; 120/80 mmHg, N = 295), and PHT (subjects with BP 120/80–140/90 mmHg N = 317). Results: Subjects with PHT were significantly older and had higher values of body mass index, waist circumference, serum total cholesterol levels, triglyceride levels, and fasting glucose levels (all p &lt; 0.001). The prevalence of metabolic syndrome was significantly higher in PHT group (4.3% vs. 30.4%, p &lt; 0,001). Serum HGF concentrations were higher in PHT subjects, but the difference was not significant (270.8 vs. 277.9 pg/ml, p = 0.651). Serum HGF concentration showed a significant positive correlation to systolic and diastolic BP in PHT (r = 0,226, p &lt; 0,05 and r = 0,232, p &lt; 0,01, respectively), but not in OBP group (p &gt; 0.05). Conclusions: Serum HGF is associated with BP in prehypertensive subjects, but not in subjects with optimal BP. In our cohort, the correlation is more pronounced for diastolic blood pressure.

Appraisal of hepatocyte growth factor signal transduction in the duality of HIV associated pre-eclampsia.

Hepatocyte Growth Factor (HGF) is a potent mitogen with a tyrosine kinase receptor (HGFR), which upon binding and activation functions to promote angiogenesis, tumorigenesis, cell growth, cell mortality and morphogenesis via the RAS/MAPK/ ERK, PI3K/ PKB/AKT and JAK/ STAT3 pathways. Both HGF and its receptor, HGFR play an essential role in human placentation and embryonic development during pregnancy. This study determines the concentration of HGF and HGFR in the synergy of HIV infection and pre-eclampsia (PE). A total sample size of n=80 (n=40 pre-eclamptic and n=40 normotensive) women was used. These were further stratified into HIV-positive and HIV-negative women. Analysis of the growth factors were performed via the Bio-Plex multiplex immunoassay method. The expression of serum HGF, based on pregnancy type irrespective of HIV status, was significantly downregulated in preeclamptic women vs normotensive women (p≤0.005). In contrast HGFR expression was similar between the latter groups (p≤0.4956). Based on HIV status, both HGF and HGFR expression showed no significant difference between HIV- positive and HIV-negative women, regardless of pregnancy type (p=0.4409; p=0.8869). There was a significant difference of HGF and HGFR across all study groups (p≤0.0001) with a moderate correlation between HGF and HGFR. This study demonstrates a downregulation of HGF expression in preeclampsia compared to normotensive pregnancies irrespective of HIV status. This decline impedes trophoblast cell survival and apoptosis via aberrant signalling pathways that contribute to defective trophoblast invasion in PE. The similarity of HGF and HGFR in HIV positive and negative groups emanates from the immune restorative effect of anti-retroviral usage.

MO091: Serum Hepatocyte Growth Factor is Associated With Albuminuria in Subjects With Optimal Blood Pressure and Untreated Arterial Hypertension

Abstract BACKGROUND AND AIMS Hepatocyte growth factor (HGF) is a pleiotropic factor that has a protective role in acute renal injury. HGF prevents the development of chronic renal fibrosis in animal models via inhibition of transforming growth factor β1 expression and consequently reduces podocyte injury and proteinuria.[1,2] Serum HGF concentration is associated with systolic arterial blood pressure (BP) and is higher in hypertensive than in normotensive individuals, especially if complications of arterial hypertension are developed.[3,4] Our aim was to determine the association of serum HGF concentration and albuminuria in normotensive subjects and subjects with untreated arterial hypertension. METHOD Data from 563 subjects (57.8% women, mean age 48 years) was analyzed. After clinical examination, fasting blood and urine samples were drawn. Albuminuria was normalized to urine creatinine and expressed as an albumin/creatinine ratio (ACR). HGF was measured using a commercial test. BP was measured according to ESH guidelines. Based on BP values, subjects were divided into two groups: OBP: subjects with optimal blood pressure (BP &amp;lt; 120/80 mmHg, N = 295), and UAH: subjects with untreated arterial hypertension (BP &amp;gt; 140/90 mmHg, N = 268). RESULTS Subjects with UAH were significantly older and had higher values of body mass index, waist circumference, serum total, and LDL-cholesterol levels, triglyceride levels, fasting glucose levels, and ACR (all P &amp;lt; 0.001). Serum HGF concentrations were also higher in UAH subjects, but the difference was not significant (270.8 versus 304.2 pg/mL, P = 0.651). Subjects with ACR &amp;gt; 30 mg/g had higher values of serum HGF concentration in comparison with subject with ACR &amp;lt; 30 mg/g in both groups, but the difference again was not significant (262.1 versus 527.8 pg/ml, P = 0.747 and 328.6 versus 843.5 pg/ml, P = 0.066, respectively). Serum HGF concentration showed a significant positive correlation to ACR in both groups (P &amp;lt; 0.05). Multivariate regression analysis showed that BP was an independent predictor of ACR increase (Beta = 0.134, P = 0.028), whereas age, sex and serum glucose were not. Serum HGF concentration was also a strong predictor of the ACR increase (Beta = 0.376, P &amp;lt; 0.001). CONCLUSION Serum HGF concentration is associated with ACR in subjects with not only untreated arterial hypertension but also optimal blood pressure. We found that HGF is an independent predictor of the ACR increase in this population.

Favorable Cardiovascular Health Is Associated With Lower Hepatocyte Growth Factor Levels in the Multi-Ethnic Study of Atherosclerosis

Introduction: Hepatocyte growth factor (HGF) is a cytokine released in response to endothelial injury and a potential biomarker of cardiovascular disease (CVD) risk. We examined the association between cardiovascular health (CVH) and HGF in a multi-ethnic cohort of adults free from CVD at baseline.Methods: This cross-sectional study conducted between 2020 and 2021 used MESA baseline examination data (2000–2002) from 6,490 US adults aged 45–84 years. The independent variable was CVH measured by the CVH score and number of ideal metrics. The score was derived from seven metrics: smoking, body mass index, physical activity, diet, total cholesterol, blood pressure and blood glucose. Each metric was scored 0 points (poor), 1 point (intermediate) and 2 points (ideal). The total CVH score ranged from 0 to 14. An inadequate score was 0–8, average, 9–10 and optimal, 11–14. The dependent variable was logarithmically transformed HGF. We used regression analyses to estimate associations between CVH and HGF adjusting for sociodemographic factors.Results: Participants' mean (SD) age was 62 (10) years. Fifty-three percent were female. A one-unit increment in the CVH score was significantly associated with 3% lower HGF levels. Average and optimal CVH scores were significantly associated with 8% and 12% lower HGF levels, respectively, compared to inadequate scores. Additionally, a greater number of ideal metrics was associated with lower HGF levels.Conclusion: Favorable CVH was significantly associated with lower HGF levels in this ethnically diverse cohort. Interventions aimed at promoting and preserving favorable CVH may reduce the risk of endothelial injury as indicated by lower serum HGF levels.

Analysis of Soluble Mesenchymal-Epithelial Transition Factor and Hepatocyte Growth Factor Serum Levels in Children With Autism Spectrum Disorder

Background: Hepatocyte Growth Factor (HGF) and its receptor, Mesothelial-Epithelial Transition (cMet) factor signaling, play an essential role in controlling synaptogenesis. Objectives: Because of the vital role of HGF and Met signaling in synaptogenesis and spatial learning function of the brain’s hippocampal region, we aimed to study the HGF and soluble cMet (s-cMet) serum levels in children with different stages of Autism Spectrum Disorders (ASD). Materials &amp; Methods: A total of 189 ASD patients (mild; n=69, moderate; n=63 and severe; n=57) and 82 control were enrolled in this project. Blood samples were collected from ASD patients referred to Pediatric Neurology Clinic, 17 Shahrivar Hospital, Rasht City, Iran, and serum concentrations of s-cMet and HGF were measured by ELISA. The control children with no clinical characteristics of ASD attended routine blood tests. Results: HGF Mean±SD serum concentration in ASD patients was 239±52.02 pg/mL compared to controls which was 360.04±71.15 pg/mL (P=0.004). Also, the Mean±SD serum concentrations of HGF in mild, moderate, and severe ASD patients were 297.54±69.82, 232.81±56.41, and 189±33.25 ng/mL, respectively, compared to control, which was 360.18±57.40. Besides, the s-cMet Mean±SD serum concentrations in ASD and controls were 143.54±32.50 and 200.25±31.16 pg/mL, respectively (P=0.005). The Mean±SD serum concentrations of s-cMet in the mild, moderate, and severe ASD patients were 172.81±37.69, 129.81±45.55, and 85.18±22.95 ng/mL, respectively, as compared to the control, which was 214.54±34.17 ng/mL. Conclusion: Serum HGF and s-cMet concentration decreased in ASD patients corresponding to disease severity. Also, detecting serum HGF and s-cMet may help classify ASD.

Serum HGF and APN2 are associated with disability worsening in SPMS

There are no reliable biomarkers that predict disability worsening in progressive Multiple Sclerosis (MS). We analyzed circulating biomarkers of hypoxia and angiogenesis in people with Secondary Progressive MS (SPMS) who participated in a clinical trial and were monitored prospectively for disability worsening. Concentrations of glucose transporter-1 (Glut-1), a marker of hypoxia, were higher in SPMS compared to controls. Moreover, low levels of angiopoietin-2 (APN2) and hepatocyte growth factor (HGF) were associated with disability worsening, while neurofilament light, an emerging biomarker in MS, was not. APN2 and HGF are neurotrophic and could be both potential biomarkers and therapeutic targets in SPMS.