Serum Hepatocyte Growth Factor Concentration Research Articles

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.

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.

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.

Overexpression of Hepatocyte growth factor and its soluble receptor (s-cMet) in the serum of patients with different grades of meningioma

ObjectivesMeningiomas are the most common primary intracranial tumor. Hepatocyte growth factor (HGF) and its receptor, cMet, were shown to be involved in meningioma. This study was aimed to determine the concentration of HGF and soluble cMet (s-cMet) in the serum of patients with different grades of meningioma. MethodsNinety serum samples from different grades of meningioma patients (42 cases of grade I, 28 grade II, 20 grade III) and 51 controls were included in this study. The serum total protein concentration (TPC) was measured by a Bio-Rad protein assay and serum concentration of HGF and s-cMet by enzyme linked immunosorbent assay (ELISA). ResultsNo significant change in the serum TPC of patients was seen as compared to controls. We also showed that serum HGF and s-cMet concentration in meningioma patients was higher than in controls. The results showed that starting from grades I to III meningioma, a significant increase in HGF and s-cMet serum concentration was observed (HGF; 380 ± 57.69, 430.27 ± 48.72, 596.36 ± 104.49 pg/ml, respectively, as compared to controls which was 327.72 ± 49.68 pg/ml and for s-cMet was 274.45 ± 45.05, 314.81 ± 38.71, 433.54 ± 51.81 ng/ml, respectively, as compared to controls which was 213.72 ± 29.13 ng/ml). The results showed that a high concentration of HGF and s-cMet is associated with advanced grades of meningioma. ConclusionIt is concluded that HGF and s-cMet serum levels increased in meningioma patients and their concentration was significantly higher in more advanced grades of the disease. It is also suggested that HGF/s-cMet might be involved in the progression of meningioma.

Measurement of Hepatocyte Growth Factor, Interleukin 6 and Tumor necrosis factor α in Acute Myocardial Infarction

Background: Early mortality rate due to acute myocardial infarction (AMI) is approximately 30%, and half of these deaths occur before reaching a hospital. The prevention and early detection play a key role in reducing mortality in AMI. Hepatocyte Growth Factor (HGF), Interleukin 6 (IL-6), and Tumor Necrosis Factor α (TNF-α) are most recent prognostic biomarkers for AMI. The present study was aimed to evaluate the level of these cytokines in AMI.&#x0D; Methods: In this case control study, 39 patients with AMI were compared with 30 healthy subjects. Age, sex and other possible confounding factors were matched. AMI diagnosis was confirmed by typical symptoms, electrocardiogram changes and serum concentration of troponin I and creatine kinase-MB. The levels of TNF-α, IL-6 an HGF at baseline and 3 and 7 days later were measured using ELISA method.&#x0D; Results: Levels of IL-6, TNF-α and HGF increased over time after AMI with ST-segment elevation in study group. The baseline IL-6 levels in AMI group were significantly higher than control group (P&lt;0.05).&#x0D; Conclusions: The results of this study suggest that baseline levels of IL-6 as well as serial changes of serum IL-6, TNF-α and HGF concentrations can be used as potential diagnostic biomarkers in AMI.

Effect of serum HGF and CK18 in patients with laryngeal cancer on postoperative prognosis

Objective: To investigate the correlation between the levels of serum cytokeratin 18 (CK18) and hepatocyte growth factor (HGF) and tumor stage and prognosis in patients with laryngeal carcinoma. Method: Patients with laryngeal cancer who were admitted to our hospital from January 2012 to December 2013 were enrolled. Blood samples were collected for CK18 and HGF detection, and postoperative prognosis data were collected at regular follow-up. Result: The serum CK18 and HGF concentration of patients with poorly differentiated tumor, high tumor grade and clinical stage were significantly higher than those with well differentiated tumor, low tumor grade and low clinical stage (P<0.05). The 5-year survival rate (69.9%) of patients with laryngeal cancer in the high CK18 group was significantly lower than that in the low CK18 group (92.3%) (P<0.05), and the 5-year survival rate (71.1%) of patients with laryngeal cancer in the high HGF group was significantly lower than that in the low HGF group (94.2%) (P<0.05). The results of univariate analysis showed that tumor type, differentiation, T grade, N grade and clinical stage affected the survival rate of patients with laryngeal cancer. Cox regression model analysis showed high CK18 and high HGF levels were risk factors for poor prognosis ［CK18 HR: 2.594 (1.558-4.318); P<0.001, HGF HR: 2.671 (1.605-4.446); P<0.001］. Conclusion:The results suggested that serum CK18 and HGF levels can be used as prognostic and disease monitoring biomarkers for laryngeal cancer.

Circulating Vascular Growth Factors and Magnetic Resonance Imaging Markers of Small Vessel Disease and Atrophy in Middle-Aged Adults.

Background and Purpose- Little is known about associations between vascular growth factors and magnetic resonance imaging (MRI) markers in midlife. We investigated the association of serum VEGF (vascular endothelial growth factor), Ang2 (angiopoietin 2), sTie2 (soluble tyrosine kinase with immunoglobulin-like and EGF-like domains 2), and HGF (hepatocyte growth factor) concentrations with MRI markers of brain aging in middle-aged adults. Methods- We evaluated 1853 participants (mean age, 46±9 years; 46% men) from the Framingham Heart Study. Serum growth factor concentrations were measured using standardized immunoassays. Outcomes included total brain, cortical and subcortical gray matter, white matter, cerebrospinal fluid, and white matter hyperintensity volumes derived from MRI; as well as fractional anisotropy in white matter tracts from diffusion tensor imaging. We related VEGF, Ang2, sTie2, and HGF to MRI measures using multivariable regression models adjusting for vascular risk factors. We tested for interactions with APOE (apolipoprotein E) genotype and CRP (C-reactive protein). Results were corrected for multiple comparisons. Results- Higher sTie2 was associated with smaller total brain (estimate by SD unit±SE=-0.08±0.02, P=0.002) and larger white matter hyperintensity (0.08±0.02, P=0.002) volumes. Furthermore, higher Ang2 (0.06±0.02, P=0.049) and HGF (0.09±0.02, P=0.001) were associated with larger cerebrospinal fluid volumes. Finally, higher Ang2 was associated with decreased fractional anisotropy, in APOE-ε4 carriers only. Conclusions- Vascular growth factors are associated with early MRI markers of small vessel disease and neurodegeneration in middle-aged adults.

Evaluation of liver function by means of serum cytokeratin 18 and hepatocyte growth factor levels in patients with obstructive jaundice

Objective: To evaluate the serum levels of cytokeratin 18 (CK18) and hepatocyte growth factor (HGF) in obstructive jaundice patients before and after treatment and thereby to detect the possible role of CK18 and HGF in patients with obstructive jaundice.Patients and methods: Forty patients who had obstructive jaundice and 40 healthy control subjects were included in the study. Patients were treated using percutaneous, endoscopic or surgical approaches. Blood samples were obtained at the day before and 7 days after the intervention for obstructive jaundice. Serum HGF and CK18 concentrations were determined by ELISA method.Results: There were statistically significant decreases in HGF, CK18, total bilirubin and direct bilirubin serum levels, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, and alkaline phosphatase activities and white blood cell count when compared with pre-treatment levels.Conclusion: Evaluating pre- and post-treatment serum HGF and CK18 levels suggested that there was an apoptosis in obstructive jaundice patients and this apoptosis decreased after the decompression of the biliary tract. We also demonstrated that HGF levels were altered at biliary obstruction compared to healthy controls and the levels of this biomarker also decreased after decompression of biliary obstruction. We concluded that these biomarkers can be used as predictors of liver injury in biliary obstruction.

The expression of serum hepatocyte growth factor in OSAHS

Objective:To investigate the clinical significance of detecting peripheral blood hepatocyte growth factor（HGF） in OSAHS patients.Method:Ninety-six cases of OSAHS patients in our hospital were selected as OSAHS group,and were divided into 3 subgroups according to the PSG results：mild,medium and severe. Each group included 32 cases,Thirty-five cases of healthy persons were selected as control group. ELISA method was utilized to detect the HGF level of peripheral blood. HGF concentration was measured in 32 patients with severe OSAHS after 3 months of comprehensive treatment. The relationship between serum HGF and sleep respiration events was further analyzed.Result: The HGF concentration of peripheral blood increased with the severity of OSAHS.The serum levels of HGF in the control,mild,medium and severe group were（487.75±46.74）pg/ml，（519.44±50.77）pg/ml，（753.52±58.91） pg/ml and（829.49±61.74）pg/ml,respectively. There were significant differences among groups（F=117．733,P<0.01). HGF concentration in peripheral blood of OSAHS patients was unrelated to sex,age,and BMI（P>0.05）,and positively correlated with AHI,negatively correlated with LSaO₂（P<0.01）. After comprehensive treatment,the serum HGF concentration and AHI in severe OSAHS group were significantly decreased,while LSaO₂ was significantly increased.Conclusion:The level of HGF was increased in OSAHS patients and was positively correlated with the severity of OSAHS. Determining the level of HGF in peripheral blood is important for evaluating the severity of OSAHS and the degree of vascular endothelial dysfunction,and assessing the risk of cardiovascular disease.

Higher Serum Hepatocyte Growth Factor Concentration is Associated with Better Preservation of GFR in Hemodialysis Patients

Background/Aims: Hemodialysis induces an intravascular inflammatory reaction which may further deteriorate renal function. We studied changes of serum interleukin 6 (IL6) and hepatocyte growth factor (HGF) concentrations during dialysis sessions, and at 12 month intervals. The synthesis of these cytokines in arterial endothelial cells in the presence of serum obtained from dialyzed patients was studied. Changes of the inflammatory reaction during 12 months of treatment were correlated with GFR. Methods: The study was performed on a group of 30 uremic patients treated with hemodialysis. Serum samples were collected before the start of dialysis, 15 minutes, and 4 hours later, when the session was finished. Serum levels of IL6 and HGF were measured with ELISA, as was the effect of serum samples on the synthesis of these cytokines in arterial endothelial cells. Results: At baseline hemodialysis induced an increase of serum IL6 (+10%) and HGF (+164%) levels at the end of the session. After 12 months of treatment predialysis serum IL 6 level was increased as compared to the beginning of the study (+22%), but no change in serum HGF level was observed. At that time the dialysis-induced rise of serum IL6 level was stronger than at the start (+18%), but the observed effect for HGF was weaker (+116%). An inverse correlation was observed between the dialysis-induced increase of HGF level and decrease of GFR after 12 months of study. The same relation was seen for HGF synthesis in the endothelium, but opposite for IL6 synthesis in the endothelium. Conclusions: We found that a higher HGF serum level during hemodialysis treatment is associated with a slower loss of residual renal function.

Abstract 4102: Effect of HGF concentrations on c-Met inhibition investigation

Abstract Tumor cells frequently harbor abnormalities in signaling pathways, leading to increased migration, invasion, survival, angiogenesis, and proliferation. C-Met is a receptor tyrosine kinase critical for embryogenesis and liver repair, and protein levels are often elevated in a large variety of tumors. C-Met is activated by the endogenous ligand Hepatocyte Growth Factor (HGF). HGF is produced by mesenchymal cells and stimulates the c-Met protein, leading to a variety of downstream signaling pathways that result in increased migration, proliferation, survival, and angiogenesis. While many tumor cells express the c-Met receptor, a number of tumor types, including glioblastoma and osteosarcoma, have been observed to co-express both HGF and c-Met. The purpose of the current study was to measure tumor cell HGF secretion in vitro, to determine HGF concentrations in vivo, and study how HGF concentrations affect tumor cell response to c-Met inhibition. Over forty cell lines were investigated for HGF secretion via ELISA of conditioned media. The small molecule c-Met inhibitor BMS-777607 was used to interrupt the c-Met axis in a select number of tumor cell lines. C3H/HeJ, nude, and Balb/c mice, were measured for serum levels of HGF. Data obtained using ELISA of conditioned media show that about one quarter of the cell lines tested secreted HGF. Cell lines tested include, but are not limited to, glioblastoma, prostate, breast, fibrosarcoma, and osteosarcoma. Migration assays were performed on several of these cell lines to determine sensitivity to BMS-777607. HGF-secreting cell lines, including the KHT, U87, U118, and OS156, are sensitive to BMS-777607 at 0.1, 1, and 10 μM. Non-HGF-secreting cell lines, such as PC-3 and MDA-MB-231, are insensitive to BMS-777607 at the same concentrations. A migration assay was performed with the PC-3 cells, with cells exposed to 0.1, 1, and 10 uM BMS-777607 while in the presence of 0, 5, 10, and 25 ng/mL HGF. These cells are not sensitive to the c-Met inhibitor at low concentrations of HGF, yet become sensitive at higher concentrations. These results indicate that sensitivity to c-Met inhibition may be dependent on both HGF-secretion status and levels of exogenous HGF. Furthermore, our findings suggest that in vitro investigations of c-Met inhibition should be done at physiologically relevant HGF concentrations. In order to properly perform c-Met inhibition experiments in vitro, a better understanding of in situ HGF concentration is needed. Serum levels of HGF were measured in the C3H/HeJ, nude, and Balb/c mice. The average serum HGF concentration in these mice was between 3 and 5 ng/mL. Still, it is ultimately the local concentration of HGF within the tumor microenvironment that is critical, but no intra-tumor values for HGF have been reported. Consequently measurements of HGF levels within tumors by microdialysis are ongoing. Citation Format: Veronica S. Hughes, Dietmar W. Siemann. Effect of HGF concentrations on c-Met inhibition investigation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4102.

Usefulness of the Hepatocyte Growth Factor as a Predictor of Mortality in Patients Hospitalized With Acute Heart Failure Regardless of Ejection Fraction

Hepatocyte growth factor (HGF) plays a role in the improvement of cardiac function and remodeling. Their serum levels are strongly related with mortality in chronic systolic heart failure (HF). The aim of this study was to study prognostic value of HGF in acute HF, interaction with ejection fraction, renal function, and natriuretic peptides. We included 373 patients (age 76 ± 10years, left ventricular ejection fraction [LVEF] 46 ± 14%, 48% men) consecutively admitted for acute HF. Blood samples were obtained at admission. All patients were followed up until death or close of study (>1year, median 371days). HGF concentrations were determined using a commercial enzyme-linked immunosorbent assay (human HGF immunoassay). The predictive power of HGF was estimated by Cox regression with calculation of Harrell C-statistic. HGF had a median of 1,942 pg/ml (interquartile rank 1,354). According to HGF quartiles, mortality rates (per 1,000 patients/year) were 98, 183, 375, and 393, respectively (p <0.001). In Cox regression analysis, HGF (hazard ratio1SD= 1.5, 95% confidence interval 1.1 to 2.1, p= 0.002) and N-terminal pro b-type natriuretic peptide (NT-proBNP; hazard ratio1SD= 1.8, 95% confidence interval 1.2 to 2.6, p= 0.002) were independent predictors of mortality. Interaction between HGF and LVEF, origin, and renal function was nonsignificant. The addition of HGF improved the predictive ability of the models (C-statistic 0.768 vs 0.741, p= 0.016). HGF showed a complementary value over NT-proBNP (p= 0.001): mortality rate was 490 with both above the median versus 72 with both below. In conclusion, in patients with acute HF, serum HGF concentrations are elevated and identify patients at higher risk of mortality, regardless of LVEF, ischemic origin, or renal function. HGF had independent and additive information over NT-proBNP.

Evaluation of serum HGF and CK18 levels in patients with esophageal cancer.

Cytokeratins are thought to play a role in apoptosis. Cytokeratin 18 (CK18) is involved in the formation of intracellular cytoskeleton, and has been considered a promising apoptosis marker in gastrointestinal carcinomas. Growth factors, including hepatocyte growth factor (HGF), may provide a microenvironment for malignant cells. In this study, we aimed to compare serum HGF and CK18 levels between esophageal squamous cell carcinoma patients and healthy controls. The study included 41 adult patients (20 male, 21 female) diagnosed with esophageal squamous cell carcinoma, with a mean age of 63.54 ± 10.88 years (range, 41-82 years). We also recruited 39 age and gender-matched healthy control subjects. Venous blood samples were taken; serum HGF and CK18 concentrations were determined via ELISA. Results indicated that serum HGF levels were higher in patients (1.37 ± 0.63 ng/mL) as compared to the healthy subjects (0.41 ± 0.29 ng/mL). Similarly, serum CK18 levels were higher in the patient group (2.53 ± 1.33 ng/mL) than in the control group (0.34 ± 0.23 ng/mL) (P < 0.001). In addition, serum HGF and CK18 levels were positively correlated with metastasis stage, tumor stage, and disease stage of esophageal squamous cell carcinoma. To our knowledge, this is the first study to evaluate serum HGF and CK18 levels in patients with esophageal squamous cell carcinoma. The results suggest that serum CK18 and HGF levels may be used as prognostic and disease monitoring biomarkers of esophageal squamous cell carcinoma.

The low levels of circulating hepatocyte growth factor in nephrolithiasis cases: independent from gene polymorphism.

Environmental and genetic factors are important in development of nephrolithiasis. In a recent study, it has been demonstrated that hepatocyte growth factor (HGF) has an anti-apoptotic effect and thus can reduce the adhesion of calcium oxalate monohydrate crystals to renal epithelial cells. The aim of this study was to evaluate the HGF serum levels and its two gene polymorphisms and possible association of the two in patients with nephrolithiasis. One hundred and five patients with nephrolithiasis and 70 healthy volunteers with similar demographic features were included in this study. Serum HGF levels were measured, and HGF intron 13 C>A (in 102 stone patients and 68 healthy subjects) and intron 14 T>C (in 99 stone patients and 56 healthy subjects) polymorphisms were determined using real-time polymerase chain reaction with TaqMan allelic discrimination method. There were no statistically significant differences in HGF intron 13 C>A and intron 14 T>C polymorphisms between the control and patient groups (X (2) = 1.72 df = 2; p = 0.42, and X (2) = 0.68 df = 2; p = 0.71, respectively). Mean serum HGF concentration was significantly lower in the stone disease patients than in the control subjects (1.05 ± 0.63 pg/mL and 1.35 ± 0.58 ng/mL respectively, p = 0.0001). When allele distribution frequency between stone patients and healthy subjects was compared, there were no significant differences in intron 13 and intron 14 allele distributions between two groups (p = 0.43 and p = 0.44, respectively). It may be concluded from the findings that decrease in HGF levels may play a role in renal stone formation, independent from gene polymorphisms.

Hepatocyte growth factor measurement in AL amyloidosis

Hepatocyte growth factor (HGF) is a pro-angiogenic cytokine activated by tissue-type plasminogen activator (tPA) that might play a role in the progression of multiple myeloma (MM). Preliminary studies indicated that serum HGF levels were higher in patients with AL amyloidosis (AL) compared to those with MM. The aim of the present study was to determine whether HGF is a relevant marker of diagnosis and prognosis in AL. HGF serum levels were measured at diagnosis in patients with monoclonal gammopathy (MG) without AL (76 controls), or with biopsy-proven systemic AL (69 patients). HGF serum levels were significantly higher in patients with AL compared to controls, respectively, 11.2 ng/mL [min: 0.95–max: 200.4] versus 1.4 ng/mL [min: 0.82–max: 6.2] (p < 0.0001). The threshold value of 2.2 ng/mL conferred optimal sensitivity (88%) and specificity (95%) to differentiate AL and monoclonal gammopathy of undetermined significance (MGUS) patients. Serum HGF concentrations were correlated positively with the severity of cardiac involvement and the serum level of monoclonal light chains. These data suggest that HGF measurement could be used in patients with MG to detect AL or to reinforce a clinical suspicion of AL and to guide indications for diagnostic tissue biopsies.

Early Pregnancy Maternal Hepatocyte Growth Factor and Risk of Gestational Diabetes.

AimsWe investigated associations of serum hepatocyte growth factor (HGF) with risk of gestational diabetes mellitus (GDM). We also examined whether pre-pregnancy overweight/obesity status or leisure-time physical activity (LTPA) modify these associations.MethodsIn a nested case-control study (173 GDM cases and 187 controls) among participants of a pregnancy cohort, early pregnancy (16 weeks of gestation, on average) serum HGF was measured using enzyme-linked immunoassay. GDM was diagnosed using American Diabetes Association guidelines. Logistic regression was used to calculate odd ratios (ORs) and 95% confidence intervals (CI). Effect modifications by pre-pregnancy overweight/obesity status or LTPA during pregnancy were examined using stratified analyses and interaction terms.ResultsOverall, we did not find significant associations of serum HGF with GDM risk (p-value> 0.05). However, compared with women who had low serum HGF concentrations (<2.29 ng/ml), women with high serum HGF concentrations (≥ 2.29 ng/ml) had 3.8-fold (95%CI: 1.30–10.98) and 4.5-fold (95%CI: 1.28–15.80) higher GDM risk among women who were overweight/obese, pre-pregnancy (body mass index≥25 kg/m2), or did not report LTPA, respectively. These associations were not present among women who were not overweight/obese (interaction p=0.05) or reported LTPA (interaction p=0.05).ConclusionOverweight/obesity status and LTPA may modify associations of early pregnancy serum HGF with subsequent GDM risk.

Association between Hepatocyte Growth Factor (HGF) Gene Polymorphisms and Serum HGF Levels in Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by proliferation and insufficient apoptosis of synovial cell, inflammatory cell infiltration, angiogenesis, and destruction of joints. Hepatocyte growth factor (HGF) has many functions, such as regulation of inflammation, angiogenesis, and inhibition of apoptosis. The purpose of this study was to investigate the association between intron 13 C/A and intron 14 T/C HGF gene polymorphisms and serum HGF levels in patients with RA. 100 patients with RA and 123 healthy controls were included in this study. Serum HGF concentrations were measured using ELISA kit. Gene polymorphisms were determined by allelic discrimination analysis using the real-time PCR method. HGF levels, frequency of AA genotype and A allele for intron 13 C/A polymorphism and frequency of CC genotype and C allele for intron 14 T/C polymorphism were increased in patients with RA compared to healthy controls. There was no overall associations between genotypes and serum HGF concentrations in both patient and control groups. Our results indicate that HGF protein and gene may play an important role in the etiopathogenesis of RA. However, further studies are required for a better understanding of mechanisms related to the disease process.

Markers of hepatic regeneration associated with surgical attenuation of congenital portosystemic shunts in dogs

Dogs with congenital portosystemic shunts (CPSS) have liver hypoplasia and hepatic insufficiency. Surgical CPSS attenuation results in liver growth associated with clinical improvement. The mechanism of this hepatic response is unknown, although liver regeneration is suspected. This study investigated whether markers of liver regeneration were associated with CPSS attenuation. Dogs treated with CPSS attenuation were prospectively recruited. Residual liver tissue was collected for gene expression analysis (seven genes) from 24 CPSS dogs that tolerated complete attenuation, 25 dogs that tolerated partial attenuation and seven control dogs. Relative gene expression was measured using quantitative polymerase chain reaction (qPCR). Blood samples were collected before, 24 h and 48 h post-surgery from 36 CPSS dogs and from 10 control dogs. Serum hepatocyte growth factor (HGF) concentration was measured using a canine specific enzyme-linked immunosorbent assay (ELISA). HGF mRNA expression was significantly decreased in CPSS compared with control dogs (P = 0.046). There were significant increases in HGF (P = 0.050) and methionine adenosyltransferase 2 A (MAT2A; P = 0.002) mRNA expression following partial CPSS attenuation. Dogs with complete attenuation had significantly greater MAT2A (P = 0.024) mRNA expression compared with dogs with partial attenuation. Serum HGF concentration significantly increased 24 h following CPSS attenuation (P < 0.001). Hepatic mRNA expression of two markers of hepatocyte proliferation (HGF and MAT2A) was associated with the response to surgery in dogs with CPSS, and serum HGF significantly increased following surgery, suggesting hepatocyte proliferation. These findings support the concept that hepatic regeneration is important in the hepatic response to CPSS surgery.

High Concentration but Low Activity of Hepatocyte Growth Factor in Periodontitis

High levels of hepatocyte growth factor (HGF), a healing factor with regenerative and cytoprotective effects, are associated with inflammatory diseases, including periodontitis. HGF biologic activity requires binding to its receptors, the proto-oncogene c-Met and heparan sulfate proteoglycan (HSPG). This study investigates HGF expression and its relationship to subgingival microbiota in medically healthy individuals with and without periodontitis. Saliva, gingival crevicular fluid (GCF), and blood samples from 30 patients with severe periodontitis and 30 healthy controls were analyzed for HGF concentration using enzyme-linked immunosorbent assay and binding affinity for HSPG and c-Met using surface plasmon resonance. The regenerative effects of saliva from three patients and controls were analyzed in an in vitro model of cell injury. Subgingival plaques were analyzed for the presence of 18 bacterial species. Patients with periodontitis showed higher HGF concentrations in saliva, GCF, and serum (P <0.001); however, the binding affinities for HSPG and c-Met were reduced in GCF and saliva (P <0.002). In contrast to the controls, saliva from patients showed no significant regenerative effect over time on gingival epithelial cells. Compared with controls, patients had a higher prevalence of periodontally related bacteria. Higher circulatory HGF levels indicate a systemic effect of periodontitis. However, the HGF biologic activity at local inflammation sites was reduced, and this effect was associated with the amount of periodontal bacteria. Loss of function of healing factors may be an important mechanism in degenerative processes in periodontally susceptible individuals.