Serum Fibroblast Growth Factor Research Articles

Circulating serum fibroblast growth factor 21 as risk and prognostic biomarker of retinal artery occlusion

To evaluate the predictive and prognostic value of fibroblast growth factor 21 (FGF21) levels in retinal artery occlusion (RAO) patients. In this case–control study, serum FGF21 levels were detected by using the ELISA method. Multivariable logistic regression analyses were performed to evaluate the significance of FGF21 in assessing the risk of developing RAO and its impact on vision and concurrent ischemic stroke. Compared with control group, serum FGF21 levels were significantly higher (median [IQR] = 230.90[167.40,332.20] pg/ml) in RAO patients. Multivariate logistic regression analysis showed that elevated serum FGF21 levels were associated with a higher risk of RAO occurrence (P = 0.025, OR [95%CI] = 9.672 [2.573, 36.359]) after adjustment for multiple confounding factors. Higher serum FGF21 levels were negatively associated with visual acuity improvement (P = 0.029, OR [95%CI] = 0.466[0.235, 0.925]) and positively correlated with concurrent ischemic stroke (P = 0.04, OR [95% CI] = 1.944[1.029, 3.672]) in RAO patients. Elevated serum FGF21 levels could promote the development of RAO and indicate worse visual prognosis and increase the risk of concurrent ischemic stroke, which might help clinicians early diagnose and treat RAO patients.

#977 Etelcalcetide improve left ventricular hypertrophy by suppressing the renin-angiotensin-aldosterone system and cardiac fibroblast growth factor 23

Abstract Background and Aims Calcimimetics are allosteric activators of the calcium-sensing receptor (CaSR) and are employed as therapeutic agents for managing secondary hyperparathyroidism in chronic kidney disease (CKD) patients undergoing dialysis. Although they have shown potential in reducing cardiovascular diseases and suppressing left ventricular hypertrophy (LVH), the mechanisms underlying these effects are not fully elucidated. In this study, we focused on exploring the mechanisms behind the suppression of LVH by calcimimetics using CKD, LVH, and CKD+LVH model rats. Specifically, we investigated the impact on CKD-mineral bone disorder (CKD-MBD) parameters, the renin-angiotensin-aldosterone system (RAAS), and calcineurin/nuclear factor of activated T cells (CaN/NFAT) pathway. Method In this study, we used etelcalcetide (ET) as a calcimimetic agent. At 8 weeks of age, LVH was induced in rats through transverse aortic coarctation, and CKD was induced by 5/6 nephrectomy at 9 and 10 weeks of age. The rats were divided into the four main groups: the sham group, the CKD group, the LVH group, and the CKD+LVH group. Each of the latter three groups were further subdivided into a vehicle-treated group and an ET-treated group for a duration of eight weeks. At 19 weeks of age, echocardiography was conducted on all rats prior to sacrifice. Subsequently, the rats were sacrificed, and blood and urine analyses, mRNA expression analysis, and renal histological analysis were performed. We evaluated LVH, CKD-MBD, RAAS, and CaN/NFAT pathways across these seven groups. Results In both the CKD and CKD+LVH groups, serum levels of parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) were significantly elevated, and these elevations were mitigated by ET. However, in the LVH group, serum PTH and FGF23 levels were not elevated, and ET did not induce any changes. No significant alterations in serum levels of phosphorus, calcium, 25(OH)vitamin, and 1,25(OH)2vitaminD levels due to ET were observed in any of the groups. Interestingly, ET suppressed the increase in myocardial weight/body weight ratios and the area of cardiomyocytes not only in the CKD and CKD+LVH group but also in the LVH group, despite no changes in serum PTH and FGF23 levels. Regarding the RAAS, ET attenuated the increase in serum aldosterone levels, expressions of cardiac angiotensin-converting enzyme (ACE), cardiac angiotensinogen, and cardiac angiotensin II in the LVH group and the CKD+LVH group. The expression of cardiac FGF23, which increased in the LVH group and the CKD+LVH group, was decreased by ET. Moreover, there was a significant correlation between cardiac RAAS parameters and cardiac FGF23 expressions. No alteration was observed in the CaN/NFAT pathway in response to ET. Conclusion Our findings indicated that ET effectively suppressed LVH in the CKD group and the CKD+LVH group, and it was also effective in the LVH group, independent of changes in serum CKD-MBD parameters. This suggests that ET may exert its LVH-suppressing effects through the RAAS pathway and cardiac FGF23.

Relationship of postprandial fibroblast growth factor 21 with lipids, inflammation and metabolic dysfunction-associated fatty liver disease during oral fat tolerance test

IntroductionMetabolic dysfunction-associated fatty liver disease (MAFLD) is closely associated with serum fibroblast growth factor (FGF) 21; however, previous studies have typically focused on the static fasting state, and the relationships between postprandial FGF21 levels, postprandial metabolic status, and MAFLD remain unclear. Therefore, we measured postprandial lipids, inflammatory factors, and FGF21 levels in MAFLD and further analyzed their relationship using an oral fat tolerance test (OFTT).Patients and methodsIn total, 103 non-diabetic adult volunteers, including 46 patients with MAFLD, were included in this study. All participants underwent the OFTT. Venous blood samples were collected at 0, 2, 4, and 6 h. Circulating total cholesterol (TC), triglyceride (TG), free fatty acid (FFA), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), hypersensitive-C reactive protein(hs-CRP) and FGF21 were assessed.ResultsSerum FGF21 significantly increased in the fasting state (P < 0.05) and showed a biphasic change of first decreasing and then increasing in MAFLD during the OFTT. The postprandial levels of TG, TC, LDL-C, FFA, IL-6, TNF-α and hs-CRP were significantly increased in MAFLD (P < 0.05). After adjusting for multiple factors, the FGF21 incremental area under the curve (iAUC) was linearly correlated with the FFA iAUC, TG iAUC, and IL-6 iAUC (P < 0.05) and was an independent factor for MAFLD (P < 0.05, OR=1.403).ConclusionDyslipidemia and excessive inflammation in MAFLD are associated to FGF21 levels in the postprandial period. An abnormal postprandial FGF21 response may be an important mechanism of MAFLD.

The importance of serum fibroblast growth factor-23 in obesity and metabolic syndrome, Potential effect of nutritional therapy intervention

The importance of serum fibroblast growth factor-23 in obesity and metabolic syndrome, Potential effect of nutritional therapy intervention

Correlation of serum fibroblast growth factor-23 levels and calcium phosphate products levels in chronic kidney disease; sub analysis of chronic kidney disease-mineral and bone disorder study

<em data-sider-select-id="0e59b1fc-fce5-41b4-b987-316daa778de4">Introduction: The body produces fibroblast growth factor-23 (FGF-23) to maintain normal phosphate levels when hyperphosphatemia occurs. Production of FGF-23 indirectly causes hypocalcemia. Phosphate and calcium disturbances also occur in chronic kidney disease (CKD), therefore this adaptation mechanism applies. This situation; however, only manifests in the early stages of CKD; if the estimated glomerular filtration rate (eGFR) is less than 30% of normal. This adaptation is no longer adequate and levels of calcium-phosphate (Ca×P) products and FGF-23 still rise. <em data-sider-select-id="f0dc3bf1-1598-419e-9de6-fe837eadc8e6">Objectives: In this study, the correlation between both the serum levels of FGF-23 and Ca×P products in CKD was analyzed. <em data-sider-select-id="a367eeb1-7c32-4bf0-98ef-e6ae52522dc7">Patients and Methods: A cross-sectional study including 78 subjects with CKD stages 3 to 5 dialysis was conducted. Serum FGF-23 levels were determined using the enzyme-linked immunosorbent assay (ELISA) method and Ca×P product levels were calculated using the formula calcium (mg/ dL) × phosphate (mg/dL). The Kolmogorov-Smirnov test and Spearman’s test were conducted in the statistical study. If the P value is less than 0.05, the statistical findings are significant. <em data-sider-select-id="e286c166-6c09-432e-b832-c902b1a13b81">Results: Serum FGF-23 levels and Ca×P product levels were shown to be significantly correlated. This analysis of the two correlations was independent of age and diabetes mellitus (DM). Based on stages of CKD, serum FGF-23 levels and Ca×P product levels were discovered to be significantly correlated only at stage 5 of non-dialysis. <em data-sider-select-id="9b3534d4-deaa-4ccf-8b82-745bb5380661">Conclusion: Increasing serum FGF-23 levels were correlated with increased Ca×P product levels, particularly in CKD stage 5 non-dialysis subjects. This correlation was independent of age and DM.

SLC25A28 Overexpression Promotes Adipogenesis by Reducing ATGL.

Adipose tissue dysfunction is seen among obese and type 2 diabetic individuals. Adipocyte proliferation and hypertrophy are the root causes of adipose tissue expansion. Solute carrier family 25 member 28 (SLC25A28) is an iron transporter in the inner mitochondrial membrane. This study is aimed at validating the involvement of SLC25A28 in adipose accumulation by tail vein injection of adenovirus (Ad)-SLC25A28 and Ad-green fluorescent protein viral particles into C57BL/6J mice. After 16 weeks, the body weight of the mice was measured. Subsequently, morphological analysis was performed to establish a high-fat diet (HFD)-induced model. SLC25A28 overexpression accelerated lipid accumulation in white and brown adipose tissue (BAT), enhanced body weight, reduced serum triglyceride (TG), and impaired serum glucose tolerance. The protein expression level of lipogenesis, lipolysis, and serum adipose secretion hormone was evaluated by western blotting. The results showed that adipose TG lipase (ATGL) protein expression was reduced significantly in white and BAT after overexpression SLC25A28 compared to the control group. Moreover, SLC25A28 overexpression inhibited the BAT formation by downregulating UCP-1 and the mitochondrial biosynthesis marker PGC-1α. Serum adiponectin protein expression was unregulated, which was consistent with the expression in inguinal white adipose tissue (iWAT). Remarkably, serum fibroblast growth factor (FGF21) protein expression was negatively related to the expansion of adipose tissue after administrated by Ad-SLC25A28. Data from the current study indicate that SLC25A28 overexpression promotes diet-induced obesity and accelerates lipid accumulation by regulating hormone secretion and inhibiting lipolysis in adipose tissue.

Relationships of serum FGF23 and α-klotho with atherosclerosis in patients with type 2 diabetes mellitus

BackgroundCompelling evidence suggests that calcium/phosphorus homeostasis-related parameters may be linked to diabetes mellitus and cardiovascular events. However, few studies have investigated the association of fibroblast growth factor 23 (FGF23), α-klotho and FGF23/α-klotho ratio with atherosclerosis in patients with type 2 diabetes mellitus (T2DM).ObjectiveThis study was designed to evaluate whether FGF23, α-klotho and FGF23/α-klotho ratio are associated with T2DM and further to explore the relationships between these three factors and atherosclerosis in Chinese patients with T2DM.MethodsSerum FGF23 and α-klotho levels were measured via an enzyme-linked immunosorbent assay (ELISA) kit, and the carotid intima-media thickness (CIMT) was assessed via high-resolution color Doppler ultrasonography. The associations of serum FGF23, α-klotho and FGF23/α-klotho ratio with atherosclerosis in T2DM patients were evaluated using multivariable logistic regression models.ResultsThis cross-sectional study involved 403 subjects (207 with T2DM and 196 without T2DM), 41.7% of the patients had atherosclerosis, and 67.2% of the carotid intima were thickened to a thickness greater than 0.9 mm. Compared with those in the lowest tertile, higher tertiles of FGF23 levels and FGF23/α-klotho ratio were positively associated with T2DM after adjusting for covariates, and serum α-klotho concentration was inversely correlated with T2DM (all P values < 0.01). Moreover, elevated serum FGF23 levels and FGF23/α-klotho ratio were positively associated with CIMT and carotid atherosclerosis in T2DM patients (all P values < 0.01). Further spline analysis similarly revealed linear dose‒response relationship (all P values < 0.01). And there was still significant differences in CIMT and carotid atherosclerosis between the highest group of α-klotho and the reference group in T2DM patients (P values = 0.05).ConclusionsT2DM was positively linearly related to serum FGF23 concentration and FGF23/α-klotho ratio, and negatively correlated with serum α-klotho concentration. Furthermore, both FGF23 and FGF23/α-klotho ratio were positively correlated with CIMT and atherosclerosis in T2DM patients, while α-klotho was inversely correlated with both CIMT and atherosclerosis, although the associations were not completely significant. Prospective exploration and potential mechanisms underlying these associations remain to be further elucidated.

ROLE OF MATERNAL SERUM FIBROBLAST GROWTH FACTOR 21 LEVEL IN PREDICTION OF PREECLAMPSIA

Pregnancy complications resulting from hypertensive disorders are a serious problem that impact 2-10 % of all pregnanciesglobally. Preeclampsia is defi ned as new onset hypertension and proteinuria after 20 weeks of gestation which may be associated with other maternal organ dysfunction, such as liver or renal insuffi ciency, hematological or neurological complications, uteroplacental dysfunction and fetal growth restriction.Aim of the Work: Primary outcome is to determine the correlation between fi broblast growth factor 21 level and preeclampsia &amp; signifi cance of serum fi broblast growth factor 21 levels as a predictive tool for preeclampsia. Secondary outcome is to establish the relationship between maternal serum fi broblast growth factor 21 level and Maternal complictions: - Eclampsia (tonic clonic fi ts after 20 weeks with elevated blood pressure and proteinuria)- HELLP syndrome (hemolysis, elevated liver enzymes and low platelet occur as a complication of severe preeclampsia)- placental abruption (bleeding after 20 weeks gestation due to premature separation of a normally situated placenta)Patients and Methods: This was a Nested case-control study that was conducted on 90 primigravidas at Ain Shams University maternity hospital from April 2021 to April 2022. Ethical approval was obtained from the ethical committee at Ain- Shams university maternity hospital. Data was recruited from patient attending obstetric clinic at Ain Shams University Maternity Hospital. Blood samples were collected after 20 weeks to 28 weeks gestation. Patients was followed up until delivery and grouped according to development of preeclampsia.Random samples from 45 patients (group who develop PE) and 45 random samples from control group were assessed forfi broblast growth factor 21. Serum fi broblast growth factor 21 levels were measured by a commercially available enzyme- linked immunosorbent assay kit.Results: our study showed that there was a significant difference in FGF21 levels between the groups, patients withpreeclampsia having higher levels than controls, 15.9 % of patients with preeclampsia experienced maternal complicationscompared to none in the control group. Meanwhile, 18.2 % of patients with preeclampsia experienced fetal complicationscompared to 0 % in the control group.Conclusion: Serum FGF-21 levels are signifi cantly higher in preeclamptic pregnant women compared to healthy normotensive pregnant women. So, it can be used as a predictor for preclampsia and maternal complicationsFunding information: The article was written and published without any fi nancial support.Confl ict of interest disclosure: The authors of the article have noconfl ict of interest related to the publication of the article

Gα11 deficiency increases fibroblast growth factor 23 levels in a mouse model of familial hypocalciuric hypercalcemia.

Fibroblast growth factor 23 (FGF23) production has recently been shown to increase downstream of Gαq/11-PKC signaling in osteocytes. Inactivating mutations in the gene encoding Gα11 (GNA11) cause familial hypocalciuric hypercalcemia (FHH) due to impaired calcium-sensing receptor signaling. We explored the effect of Gα11 deficiency on FGF23 production in mice with heterozygous (Gna11+/-) or homozygous (Gna11-/-) ablation of Gna11. Both Gna11+/- and Gna11-/- mice demonstrated hypercalcemia and mildly raised parathyroid hormone levels, consistent with FHH. Strikingly, these mice also displayed increased serum levels of total and intact FGF23 and hypophosphatemia. Gna11-/- mice showed augmented Fgf23 mRNA levels in the liver and heart, but not in bone or bone marrow, and also showed evidence of systemic inflammation with elevated serum IL-1β levels. Furin gene expression was significantly increased in the Gna11-/- liver, suggesting enhanced FGF23 cleavage despite the observed rise in circulating intact FGF23 levels. Gna11-/- mice had normal renal function and reduced serum levels of glycerol-3-phosphate, excluding kidney injury as the primary cause of elevated intact FGF23 levels. Thus, Gα11 ablation caused systemic inflammation and excess serum FGF23 in mice, suggesting that patients with FHH - at least those with GNA11 mutations - may be at risk for these complications.

Serum fibroblast growth factor 19 level correlates inversely with clinical and endoscopic activity of inflammatory bowel disease.

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic condition with relapsing-remitting course. Diarrhea and abdominal pain are the most common IBD symptoms. Fibroblast growth factor 19 (FGF19) is an endocrine factor that inhibits hepatic bile acid production and may be used as a diagnostic marker for bile acid malabsorption. To assess serum FGF19 levels in active and inactive phases of IBD and find a potential correlation between FGF19 and disease activity. Fasting serum FGF19 levels were measured in 105 IBD patients (47 UC patients, 41 CD patients without previous ileocecal resection (NR-CD), 17 CD patients after ileocecal resection (IR-CD), and 17 control subjects). The disease activity was assessed using clinical, laboratory and endoscopic criteria. Inverse correlations were found between FGF19 level and intensity of diarrhea (in UC), abdominal pain intensity (in UC and IR-CD) and inflammatory markers (in UC and IR-CD). Moreover, FGF19 concentration was inversely correlated with clinical and endoscopic activity indices in UC and CD. Fluctuations in FGF19 level related to clinical and endoscopic activity of UC and CD revealed a clear pattern of higher values in remission than in active disease phases. Fibroblast growth factor 19 may serve as a potential diagnostic biomarker and constitute a new therapeutic target in IBD.

High Fibroblast Growth Factor 23, Sialic Acids, and Albumin Modulation in Alzheimer’s Patients

Background: Alzheimer’s disease (AD) is a prevalent form of dementia, posing significant health and societal burdens. Pathologically characterized by neurofibrillary tangles and senile plaques, it lacks definitive diagnostic markers. Fibroblast growth factor (FGF)23 and Sialic Acids (Sias) are implicated in cell signaling and antioxidative defense, while lipid peroxidation (LPO) is linked to neurodegeneration. The aim of this study was to assess serum levels of Fibroblast Growth Factor 23 (FGF23), Malondialdehyde (MDA) as a marker of lipid peroxidation, Sialic Acids (Sias), and albumin in Alzheimer's disease (AD) patients compared to age-matched healthy controls. Method: A case-control study involving 17 AD patients and 17 healthy controls investigated serum levels of FGF23, Sias, malondialdehyde (MDA), and albumin. Biochemical assays and statistical analyses were conducted. Results: Biochemical analyses revealed a significant increase in serum FGF23 and MDA levels in AD patients compared to controls (p &lt; 0.05). Additionally, AD patients exhibited lower levels of serum Sias and albumin. Furthermore, in the patient group, serum MDA levels were inversely correlated with normalized global gray matter volume (GMV), adjusted for age, sex, and Child-Pugh class. Conclusion: This study underscores the potential of FGF23, MDA, Sias, and albumin as biomarkers for AD. Further research elucidating their roles in AD pathogenesis is warranted. Decreased FGF23 in AD may involve disrupted phosphate regulation and neuroprotection mechanisms. Elevated MDA suggests increased lipid peroxidation, contributing to neuronal damage. Reduced Sias may impair antioxidative defense, exacerbating oxidative stress. Low albumin levels correlate with cognitive decline and oxidative damage in AD.

Assessment of Serum Fibroblast Growth factor 19 and Des-gamma Carboxy Prothrombin for Early Diagnosis of Hepatocellular Carcinoma

Assessment of Serum Fibroblast Growth factor 19 and Des-gamma Carboxy Prothrombin for Early Diagnosis of Hepatocellular Carcinoma

Serum fibroblast growth factor 23 concentration and the risk of mortality in patients undergoing peritoneal dialysis.

Fibroblast growth factor 23 (FGF23) is a phosphate-regulating hormone that is secreted in large amounts early in chronic kidney disease. In this cohort, we aimed to investigate the association between serum FGF23 concentration and mortality in patients undergoing peritoneal dialysis (PD). Serum FGF23 level was determined by enzyme-linked immunosorbent assay (ELISA) in a large 15-year prospective cohort study of PD patients with stored serum samples at baseline. Kaplan-Meier survival curves and Cox proportional hazards models were performed to characterise the relationship of FGF23 with mortality. A total of 737 incident PD patients were analysed. The baseline median FGF23 concentration was 683.2 (518.5-896.2) pg/mL. Age, serum phosphorus, high-density lipoprotein cholesterol and high-sensitivity C-reactive protein were independently correlated with serum FGF23 concentration. During a median follow-up of 66.7 (41.1-95.4) months, 171 of the 737 participants (23.2%) died, including 84 (49.1%) cardiovascular disease-related and 50 (29.2%) infection-related deaths. Multivariable Cox regression analysis showed that the adjusted hazard ratios of the highest tertile of serum FGF23 compared with those in the lowest tertile were 1.36 (95% confidence interval (CI): 0.89-2.07; p = 0.154), 0.75 (95% CI: 0.40-1.38; p = 0.353) and 2.66 (95% CI: 1.15-6.15; p = 0.022) for all-cause, cardiovascular disease-related and infection-related mortality, respectively. High serum FGF23 concentration is associated with a higher risk of infection-related death for incident PD patients.

Diabetes mellitus modifies the association between chronic kidney disease-mineral and bone disorder biomarkers and aortic stiffness in peritoneal dialysis patients.

This study aimed to investigate the relationship of four chronic kidney disease-mineral and bone disorder (CKD-MBD) biomarkers, including intact parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), soluble klotho, and fetuin-A, with aortic stiffness in peritoneal dialysis (PD) patients, comparing those with and without diabetes mellitus (DM). A total of 213 patients (mean age 58 ± 14years; 81 (38.0%) patients with DM) were enrolled. Their aortic pulse wave velocity (PWV) was measured using pressure applanation tonometry, while serum intact PTH, FGF23, α-klotho, and fetuin-A levels were measured using enzyme-linked immunosorbent assay. Overall, patients with DM had higher aortic PWV than those without (9.9 ± 1.8 vs. 8.6 ± 1.4m/s, p < 0.001). Among the four CKD-MBD biomarkers, FGF23 levels were significantly lower in DM group (462 [127-1790] vs. 1237 [251-3120] pg/mL, p = 0.028) and log-FGF23 independently predicted aortic PWV in DM group (β: 0.61, 95% confidence interval: 0.06-1.16, p = 0.029 in DM group; β: 0.10, 95% confidence interval: - 0.24-0.45, p = 0.546 in nonDM group; interaction p = 0.016). In conclusion, the association between FGF23 and aortic PWV was significantly modified by DM status in PD patients.

Serum α-Klotho and fibroblast growth factor 23 levels are not associated with non-proliferative diabetic retinopathy in type 1 diabetes mellitus.

Diabetic retinopathy is a commonly observed cause of blindness and is a common problem in individuals with diabetes. Recent investigations have showed the capability of serum α-Klotho and FGF 23 in mitigating the effects of diabetic retinopathy. This study aimed to discover the correlation between FGF 23, α-Klotho, and diabetic retinopathy in type 1 diabetics. This case-control study included 63 diabetic patients and 66 healthy controls. Following an overnight duration of fasting, morning blood samples were taken from both the patient and the control groups. The serum concentrations of α-Klotho and FGF 23 were quantified. An experienced ophthalmologist inspected the retinopathy. All participants in this study have moderate non-proliferative retinopathy. A p value under 0.05 was considered statistically significant. The mean α-Klotho level for retinopathic diabetic patients was 501.7 ± 172.2pg/mL and 579.6 ± 312.1pg/mL for non-retinopathic diabetic patients. In comparison, α-Klotho level of the control group was 523.2 ± 265.4pg/mL (p = 0.531). The mean of FGF 23 level did not demonstrate a significant difference (p = 0.259). The mean FGF 23 level were 75.7 ± 14.0pg/mL, 74.0 ± 14.8pg/mL and 79.3 ± 14.4pg/mL in groups, respectively. In conclusion, there was no significant difference in FGF 23 and α-Klotho levels between type 1 diabetics with and without retinopathy when compared to the control group.

Serum fibroblast growth factor-2 levels complement vital biomarkers for diagnosing heart failure

BackgroundEarly diagnosis of atrial fibrillation is important as it is crucial for improving patient outcomes. Fibroblast growth factor-2 (FGF2) may serve as a diagnostic biomarker for heart failure due to its ability to promote cardiac fibrosis and hypertrophy; however, the relationship between FGF2 concentration and heart failure is unclear. Therefore, this study aimed to explore whether FGF2 could aid in distinguishing patients with heart failure from healthy controls and those with dyspnea without heart failure. Additionally, to evaluate the possible correlation between serum FGF2 levels and its diagnostic parameters in patients with heart failure.MethodsPlasma FGF2 concentration was measured in 114 patients with a complaint of dyspnea (enrolled in the study between January 2022 and August 2022). Based on heart failure diagnosis, the patients were assigned to three groups, as follows: heart failure (n = 80), non-heart-failure dyspnea (n = 34), and healthy controls (n = 36), following physical examination. Possible correlations between serum FGF2 levels and other prognostic parameters in patients with heart failure were analyzed.ResultsSerum FGF2 levels were higher in patients with heart failure (125.60 [88.95, 183.40] pg/mL) than in those with non-heart-failure dyspnea (65.30 [28.85, 78.95] pg/mL) and healthy controls (78.90 [60.80, 87.20] pg/mL) (p < 0.001). Receiver operating characteristic curve analysis identified FGF2 concentration as a significant predictor in heart failure diagnosis, with an area under the curve of 0.8693 (p < 0.0001). Importantly, in the heart failure group, serum FGF2 concentrations correlated with key prognostic parameters for heart failure, such as reduced left ventricular ejection fraction and elevated serum levels of N-terminal pro-B-type natriuretic peptide.ConclusionsElevated serum FGF2 level is strongly associated with an increased risk of heart failure and could serve as a useful biomarker to complement vital diagnostic parameters for heart failure.

The role of fibroblast growth factor-2 in the development of bronchopulmonary dysplasia in very and extremely low birth weight infants

Introduction and objective: The aim of the study was to assess the association between serum levels of fibroblast growth factor-2 (FGF-2) in infants in the first week of life and the risk of developing bronchopulmonary dysplasia. Materials and methods: The study included 103 infants, born before 32 weeks of gestation with a birth weight ≤1,500 g. Serum FGF-2 levels were measured in all newborns on days 1 and 7 of life. Results: Analysing the dynamics of changes in serum FGF-2 level, a statistically significant positive correlation was observed for birth weight (R = 0.20, p = 0.0423) in the first week of life. However, no statistically significant correlation was found for gestational age (R = 0.06, p = 0.5146). Infants with bronchopulmonary dysplasia had significantly lower gestational age than those without bronchopulmonary dysplasia (p &lt; 0.0001) and birth weight (p &lt; 0.0001). No statistically significant correlation was found between the dynamics of changes in serum FGF-2 level in the first week of life and the risk of bronchopulmonary dysplasia development for the definition of bronchopulmonary dysplasia on day 28 of life (p = 0.5330), and for the definition as the need for supplemental oxygen and/or respiratory support at 36 weeks of postmenstrual age (p = 0.7914). Conclusions: The study found no association between the serum FGF-2 level in the first week of life and the risk of bronchopulmonary dysplasia development in infants born before 32 weeks of gestation with a birth weight ≤1,500 g. In the study group, a statistically significant positive correlation was found for birth weight. In our study, gestational age and birth weight were found to be among the major risk factors for the development of bronchopulmonary dysplasia.

Spectrum of PHEX Mutations and FGF23 Profiles in a Taiwanese Cohort With X-Linked Hypophosphatemia Including 102 Patients.

X-linked hypophosphatemia (XLH), the most common form of hereditary rickets, results from loss-of-function mutations in the phosphate-regulating PHEX gene. Elevated fibroblast growth factor 23 (FGF23) contributes to hypophosphatemia in XLH. This study aimed to characterize PHEX variants and serum FGF23 profiles in Taiwanese patients with XLH. We retrospectively reviewed the records of 102 patients clinically suspected of having hypophosphatemic rickets from 2006 to 2022. Serum intact Fibroblast growth factor-23 (iFGF23) levels were measured on clinic visit days. PHEX mutations were identified using Sanger sequencing, and negative cases were analyzed using whole-exome sequencing. The majority (92.1%) of patients exhibited elevated FGF23 compared with normal individuals. Among 102 patients, 44 distinct PHEX mutations were identified. Several mutations recurred in multiple unrelated Taiwanese families. We discovered a high frequency of novel PHEX mutations and identified variants associated with extreme FGF23 elevation and tumorigenesis. Our findings revealed the PHEX genotypic variants and FGF23 levels in Taiwanese patients with XLH. These results are crucial given the recent approval of burosumab, a monoclonal FGF23 antibody, for XLH therapy. This study provides key insights into the clinical management of XLH in Taiwan.

FGF23 directly inhibits osteoprogenitor differentiation in Dmp1-knockout mice.

Fibroblast growth factor 23 (FGF23) is a phosphate-regulating (Pi-regulating) hormone produced by bone. Hereditary hypophosphatemic disorders are associated with FGF23 excess, impaired skeletal growth, and osteomalacia. Blocking FGF23 became an effective therapeutic strategy in X-linked hypophosphatemia, but testing remains limited in autosomal recessive hypophosphatemic rickets (ARHR). This study investigates the effects of Pi repletion and bone-specific deletion of Fgf23 on bone and mineral metabolism in the dentin matrix protein 1-knockout (Dmp1KO) mouse model of ARHR. At 12 weeks, Dmp1KO mice showed increased serum FGF23 and parathyroid hormone levels, hypophosphatemia, impaired growth, rickets, and osteomalacia. Six weeks of dietary Pi supplementation exacerbated FGF23 production, hyperparathyroidism, renal Pi excretion, and osteomalacia. In contrast, osteocyte-specific deletion of Fgf23 resulted in a partial correction of FGF23 excess, which was sufficient to fully restore serum Pi levels but only partially corrected the bone phenotype. In vitro, we show that FGF23 directly impaired osteoprogenitors' differentiation and that DMP1 deficiency contributed to impaired mineralization independent of FGF23 or Pi levels. In conclusion, FGF23-induced hypophosphatemia is only partially responsible for the bone defects observed in Dmp1KO mice. Our data suggest that combined DMP1 repletion and FGF23 blockade could effectively correct ARHR-associated mineral and bone disorders.

Changes of FGF23 and hearing in chronic renal failure and their correlation analysis

BackgroundTo explore the association between fibroblast growth factor 23 (FGF23) and hearing in chronic renal failure (CRF). MethodsPure tone audiometry was used to detect the hearing of patients with CRF; the level of serum FGF23, creatinine, blood urea nitrogen (BUN), parathyroid hormone (PTH), and mean binaural hearing threshold were compared to the control group (people without kidney disease). The rat model of renal failure was established by 5/6 nephrectomy, and the auditory brainstem response (ABR) of rats after modeling was detected by the Tucker Davis Technologies (TDT) system; the expression level of FGF23 in the peripheral blood, renal and cochlear tissue was also detected. ResultsThe incidence of hearing loss (HL) and serum FGF23 were higher in CRF patients than the control group; the sFGF23 was positively correlated with the mean binaural hearing threshold. Animal studies showed that the ABR threshold, creatinine, FGF23, BUN, and PTH increased after modeling; although, an increase in FGF23 was observed earlier than other indicators. The HL of rats with renal failure was significantly correlated with BUN, phosphate, PTH, sFGF23, kFGF23/β-actin, eFGF23/β-actin, weight, and modeling cycle. ConclusionsBoth CRF patients and rat models showed high-frequency HL. FGF23 was highly expressed in the serum of HL renal failure patients and rats, as well as in the renal tissue and cochlea of renal failure rats. Therefore, FGF23 may be involved in the occurrence and development of HL caused by CRF.