Effects of fibroblast growth factor 21 on cell damage in vitro and atherosclerosis in vivo

2014 ◽  
Vol 92 (11) ◽  
pp. 927-935 ◽  
Author(s):  
Wenhe Zhu ◽  
Changwen Wang ◽  
Lei Liu ◽  
Yan Li ◽  
Xiaokun Li ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Cell Damage ◽  
Density Lipoprotein ◽  
Serum Levels ◽  
Lipoprotein Cholesterol ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth

Fibroblast growth factor 21 (FGF-21), which is a modulator of glucose and lipid homeostasis, acts as a novel therapeutic reagent for many metabolic perturbations. However, its potential as a treatment for cardiovascular disease, especially atherosclerosis (AS) has not been fully explored. Here, we report that recombinant FGF-21 improves resistance to cell damage from oxidative stress in vitro, and from atherosclerosis in vivo. Human umbilical vein endothelial cells (HUVECs) were induced with H2O2, followed by treatment with high purity recombinant FGF-21. The results indicated that FGF-21 significantly enhanced cell viability and decreased the degree of DNA fragmentation in HUVECs, as caused by H2O2 stress induction. Further studies revealed that FGF-21 inhibited H2O2-induced cell apoptosis by preventing the activation of mitogen-activated protein kinase (MAPK) signaling pathways. In an established rat model, FGF-21 dramatically improved the condition of atherosclerotic rats by decreasing serum levels of total triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and total cholesterol (TC), and by increasing the serum levels of high density lipoprotein cholesterol (HDL-C). FGF-21 also has antioxidant effects in the atherosclerotic rat, such that increased levels of superoxide dismutase, reduced glutathione, and reduced malondialdehyde were observed. These data provide novel insight into the potential use of FGF-21 in the prevention and treatment of human cardiovascular diseases.

scholarly journals Orphan Nuclear Receptor Nur77 Mediates Fasting-Induced Hepatic Fibroblast Growth Factor 21 Expression

Endocrinology ◽  
2014 ◽  
Vol 155 (8) ◽  
pp. 2924-2931 ◽  
Author(s):  
Ae-Kyung Min ◽  
Kwi-Hyun Bae ◽  
Yun-A Jung ◽  
Yeon-Kyung Choi ◽  
Mi-Jin Kim ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Nuclear Receptor ◽  
Fibroblast Growth Factor 21 ◽  
Orphan Nuclear Receptor ◽  
Fibroblast Growth ◽  
Cultured Hepatocytes ◽  
Fgf21 Expression

The fasting-induced hepatic hormone, fibroblast growth factor 21 (FGF21), is a potential candidate for the treatment of metabolic syndromes. Although peroxisome proliferator-activated receptor (PPAR)α is known to play a major role in the induction of hepatic FGF21 expression, other fasting-induced transcription factors that induce FGF21 expression have not yet been fully studied. In the present study, we investigated whether the fasting-induced activation of the orphan nuclear receptor Nur77 increases hepatic FGF21 expression. We found that fasting induced hepatic Nur77 and FGF21 expression. Glucagon and forskolin increased Nur77 and FGF21 expression in vivo and in vitro, respectively, and adenovirus-mediated overexpression of Nur77 (Ad-Nur77) increased FGF21 expression in vitro and in vivo. Moreover, knockdown of endogenous Nur77 expression by siRNA-Nur77 abolished the effect of forskolin on FGF21 expression. The results of ChIP assays, EMSA, and mutagenesis analysis showed that Nur77 bound to the putative NBRE of the FGF21 promoter in cultured hepatocytes and fasting induced Nur77 binding to the FGF21 promoter in vivo. Knockdown of PPARα partially inhibited forskolin-induced FGF21 expression, suggesting PPARα involvement in glucagon-stimulated FGF21 expression. In addition, double knockdown of PPARα and Nur77 further diminished FGF21 expression in cultured hepatocytes. In conclusion, this study shows that Nur77 mediates fasting-induced hepatic FGF21 expression, and suggests an alternative mechanism via which hepatic FGF21 transcription is mediated under fasting conditions.

scholarly journals Fibroblast Growth Factor 21 Ameliorates Hyperuricemic Nephropathy By Improving Oxidative Stress Through Activating Akt/Nrf2 Signaling Pathway

2021 ◽  
Author(s):  
Xinghao Jiang ◽  
Yimeng Zou ◽  
Yeboah Kwaku opoku ◽  
Shijie Liu ◽  
Dan Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Therapeutic Effect ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Glomerular Mesangial Cells ◽  
Nrf2 Signaling Pathway

Abstract Epidemiological investigations have shown an elevated expression of circulating fibroblast growth factor 21 (FGF21) of patients with hyperuricemia. However, the effect of FGF21 on hyperuricemic nephropathy (HN) is still unknown. The purpose of this study, therefore, was to explore the effect and mechanism of action of FGF21 on HN. The level of FGF21 in peripheral blood mononuclear cells (PBMCs) was determined in 10 patients with HN. In vivo models of HN were induced in C57BL/6 mice. Six mice in each group were treated with FGF21 at a dose of 1mg/kg and 5mg/kg for 30 days. For the in vitro studies, glomerular mesangial cells (GMCs) were exposed to lipopolysaccharide and monosodium uric acid to induce inflammation and oxidative stress. This was followed by treatment with 100nM, 1000nM of FGF21 for 72 h to observe the therapeutic effect. The levels of FGF21 in patients with HN were elevated. Also, we found that exogenous injection of FGF21 could significantly improve kidney injury in HN mice. This was characterized by a decrease in inflammatory factors and fibrosis and the improvement of oxidative stress. FGF21 recorded a significant therapeutic effect through the activation of Nrf2 in both in vivo and in vitro studies. However, the effect of enhancement of FGF21 on Nrf2 was reduced by the addition of Akt inhibitor GSK690693. In conclusion, our study found for the first time that FGF21 can significantly improve HN through the promotion of the Akt/Nrf2 signalling pathway leading to improvement in oxidative stress.

scholarly journals Fibroblast growth factor 21 (FGF21) alleviates senescence, apoptosis, and extracellular matrix degradation in osteoarthritis via the SIRT1-mTOR signaling pathway

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Hongwei Lu ◽  
Chao Jia ◽  
Dengying Wu ◽  
Haidong Jin ◽  
Zeng Lin ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Mtor Signaling Pathway ◽  
Autophagy Flux ◽  
In Vivo Experiments

AbstractOsteoarthritis (OA) is a complex condition that involves both apoptosis and senescence and currently cannot be cured. Fibroblast growth factor 21 (FGF21), known for its role as a potent regulator of glucose and energy metabolism, protects from various diseases, possibly by mediating autophagy. In the present study, the role of FGF21 in the progression of OA was investigated in both in vitro and in vivo experiments. In vitro, the results revealed that FGF21 administration alleviated apoptosis, senescence, and extracellular matrix (ECM) catabolism of the chondrocytes induced by tert-butyl hydroperoxide (TBHP) by mediating autophagy flux. Furthermore, CQ, an autophagy flux inhibitor, could reverse the protective effect of FGF21. It was observed that the FGF21-induced autophagy flux enhancement was mediated by the nuclear translocation of TFEB, which occurs due to the activation of the SIRT1-mTOR signaling pathway. The in vivo experiments demonstrated that FGF21 treatment could reduce OA in the DMM model. Taken together, these findings suggest that FGF21 protects chondrocytes from apoptosis, senescence, and ECM catabolism via autophagy flux upregulation and also reduces OA development in vivo, demonstrating its potential as a therapeutic agent in OA.

scholarly journals Dynamic changes of podocytes caused by fibroblast growth factor 2 in culture

2021 ◽  
Author(s):  
Eishin Yaoita ◽  
Masaaki Nameta ◽  
Yutaka Yoshida ◽  
Hidehiko Fujinaka
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 2 ◽  
Quiescent State ◽  
Fibroblast Growth ◽  
Gene Expressions ◽  
Dynamic Changes ◽  
Ki 67

AbstractFibroblast growth factor 2 (FGF2) augments podocyte injury, which induces glomerulosclerosis, although the mechanisms remain obscure. In this study, we investigated the effects of FGF2 on cultured podocytes with interdigitating cell processes in rats. After 48 h incubation with FGF2 dynamic changes in the shape of primary processes and cell bodies of podocytes resulted in the loss of interdigitation, which was clearly shown by time-lapse photography. FGF2 reduced the gene expressions of constituents of the slit diaphragm, inflections of intercellular junctions positive for nephrin, and the width of the intercellular space. Immunostaining for the proliferation marker Ki-67 was rarely seen and weakly stained in the control without FGF2, whereas intensely stained cells were frequently found in the presence of FGF2. Binucleation and cell division were also observed, although no significant increase in cell number was shown. An in vitro scratch assay revealed that FGF2 enhanced migration of podocytes. These findings show that FGF2 makes podocytes to transition from the quiescent state into the cell cycle and change their morphology due to enhanced motility, and that the culture system in this study is useful for analyzing the pathological changes of podocytes in vivo.

scholarly journals HIGHER SERUM LEVELS OF FIBROBLAST GROWTH FACTOR 21 IN GERIATRIC PATIENTS WITH CACHEXIA

2018 ◽  
Vol 2 (suppl_1) ◽  
pp. 300-300
Author(s):  
K Franz ◽  
M Ost ◽  
C Herpich ◽  
L Otten ◽  
V Coleman ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Geriatric Patients ◽  
Serum Levels ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth

Evaluation of the bioactivity about anti-sca-1/basic fibroblast growth factor-urinary bladder matrix scaffold for pelvic reconstruction

2018 ◽  
Vol 33 (6) ◽  
pp. 808-818 ◽  
Author(s):  
Jiankui Li ◽  
Xi Chen ◽  
Kaijian Ling ◽  
Zhiqing Liang ◽  
Huicheng Xu
Keyword(s):  
Growth Factor ◽  
Urinary Bladder ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Pelvic Organ ◽  
Fibroblast Growth ◽  
Pelvic Reconstruction ◽  
Urinary Bladder Matrix

Introduction and hypothesis: Pelvic support structure injury is the major cause of pelvic organ prolapse. At present, polypropylene-based filler material has been suggested as a common method to treat pelvic organ prolapse. However, it cannot functionally rehabilitate the pelvic support structure. In addition to its poor long-term efficiency, the urinary bladder matrix was the most suitable biological scaffold material for pelvic floor repair. Here, we hypothesize that anti-sca-1 monoclonal antibody and basic fibroblast growth factor were cross-linked to urinary bladder matrix to construct a two-factor bioscaffold for pelvic reconstruction. Methods Through a bispecific cross-linking reagent, sulfosuccinimidyl 4-[N-maleimidomethyl] cyclohexane-1-carboxylate (sulfo-smcc) immobilized anti-sca-1 and basic fibroblast growth factor to urinary bladder matrix. Then scanning electron microscope and plate reader were used to detect whether the anti-sca-1/basic fibroblast growth factor-urinary bladder matrix scaffold was built successfully. After that, the capacity of enriching sca-1 positive cells was measured both in vitro and in vivo. In addition, we evaluated the differentiation capacity and biocompatibility of the scaffold. Finally, western blotting was used to detect the level of fibulin-5 protein. Results The scanning electron microscope and plate reader revealed that the double-factor biological scaffold was built successfully. The scaffold could significantly enrich a large number of sca-1 positive cells both in vitro and in vivo, and obviously accelerate cells and differentiate functional tissue with good biocompatibility. Moreover, the western blotting showed that the scaffold could improve the expression of fibulin-5 protein. Conclusion The anti-sca-1/basic fibroblast growth factor-urinary bladder matrix scaffold revealed good biological properties and might serve as an ideal scaffold for pelvic reconstruction.

scholarly journals Thyroid hormone receptor regulates most genes independently of fibroblast growth factor 21 in liver

2014 ◽  
Vol 224 (3) ◽  
pp. 289-301 ◽  
Author(s):  
Aijun Zhang ◽  
Douglas H Sieglaff ◽  
Jean Philippe York ◽  
Ji Ho Suh ◽  
Stephen D Ayers ◽  
...  
Keyword(s):  
Growth Factor ◽  
Thyroid Hormone ◽  
Fibroblast Growth Factor ◽  
Thyroid Hormone Receptor ◽  
Expression Profiles ◽  
Fibroblast Growth Factor 21 ◽  
Small Subset ◽  
Fibroblast Growth ◽  
Serum Triglycerides

Thyroid hormone (TH) acts through specific receptors (TRs), which are conditional transcription factors, to induce fibroblast growth factor 21 (FGF21), a peptide hormone that is usually induced by fasting and that influences lipid and carbohydrate metabolism via local hepatic and systemic endocrine effects. While TH and FGF21 display overlapping actions when administered, including reductions in serum lipids, according to the current models these hormones act independentlyin vivo. In this study, we examined mechanisms of regulation of FGF21 expression by TH and tested the possibility that FGF21 is required for induction of hepatic TH-responsive genes. We confirm that active TH (triiodothyronine (T3)) and the TRβ-selective thyromimetic GC1 increase FGF21 transcript and peptide levels in mouse liver and that this effect requires TRβ. T3also induces FGF21 in cultured hepatocytes and this effect involves direct actions of TRβ1, which binds a TRE within intron 2 of FGF21. Gene expression profiles of WT andFgf21-knockout mice are very similar, indicating that FGF21 is dispensable for the majority of hepatic T3gene responses. A small subset of genes displays diminished T3response in the absence of FGF21. However, most of these are not obviously directly involved in T3-dependent hepatic metabolic processes. Consistent with these results, T3-dependent effects on serum cholesterol are maintained in theFgf21−/−background and we observe no effect of theFgf21-knockout background on serum triglycerides and glucose. Our findings indicate that T3regulates the genes involved in classical hepatic metabolic responses independently of FGF21.

Higher serum levels of fibroblast growth factor 21 in old patients with cachexia

Nutrition ◽  
2019 ◽  
Vol 63-64 ◽  
pp. 81-86 ◽  
Author(s):  
Kristina Franz ◽  
Mario Ost ◽  
Lindsey Otten ◽  
Catrin Herpich ◽  
Verena Coleman ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Serum Levels ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Old Patients
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