scholarly journals Effect of Fibroblast Growth Factor 21 on the Expression of TLR4 and BAMBI Genes in Cholesterol-Treated Human Hepatic Stellate Cells

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Elham Shakerian ◽  
Narges Mohammad Taghvaei ◽  
Zohre Askari ◽  
Reza Afarin
Keyword(s):  
Growth Factor ◽  
Mrna Expression ◽  
Fibroblast Growth Factor ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Fibroblast Growth Factor 21 ◽  
Control Group ◽  
Type I ◽  
Fibroblast Growth ◽  
Human Hscs

Background: Activated hepatic stellate cells (HSCs) are the primary mediators in the progression of hepatic fibrosis. The activation of toll-like receptor 4 (TLR4) signaling leads to the downregulation of the transmembrane inhibitory transforming growth factor-beta (TGF-β) pseudoreceptor BMP and activin membrane-bound inhibitor (BAMBI) on HSCs. Fibroblast growth factor 21 (FGF21) is a natural secretory protein in the body with effects, such as the reduction of fat accumulation and oxidation of lipids; however; no study has investigated FGF21 ability to prevent the progression of liver fibrosis. Objectives: This study aimed to examine the beneficial effects of FGF21 to reduce cholesterol-activated human HSCs. Methods: The human HSCs were incubated in media containing different concentrations of cholesterol, including 25, 50, 75, 100, 125, and 150 μM, for 24 h and then incubated with FGF21 for 24 h. Total ribonucleic acids were extracted and reversely transcribed into complementary deoxyribonucleic acid. A quantitative real-time polymerase chain reaction was performed in this study. Results: The results showed that the messenger ribonucleic acid (mRNA) expression of TGF-β, collagen, type I, alpha 1 (collagen1α), and TLR4 genes increased significantly in the presence of cholesterol (75 and 100 μM), compared to that of the control group (* P < 0.05, ** P < 0.01, and *** P < 0.001); nevertheless, the mRNA expression of the BAMBI gene significantly reduced, compared to that of the control group (* P < 0.05). The FGF21 significantly reduced the mRNA expression of TGF-β, collagen1α, and TLR4 genes (# P < 0.05). The mRNA expression of the BAMBI gene significantly increased with FGF21 (# P < 0.05). Conclusions: It was concluded that the treatment with FGF21 reduces the cholesterol-activated HSCs by decreasing the mRNA expression of the TLR4, TGF-β, and collagen1α genes and increasing the mRNA expression of the BAMBI gene.

Fibroblast Growth Factor 21 in Patients with Acromegaly

2017 ◽  
Vol 125 (10) ◽  
pp. 649-654 ◽  
Author(s):  
Jowita Halupczok-Żyła ◽  
Aleksandra Jawiarczyk-Przybyłowska ◽  
Marek Skrzypski ◽  
Mathias Strowski ◽  
Marek Bolanowski
Keyword(s):  
Growth Factor ◽  
Disease Activity ◽  
Fibroblast Growth Factor ◽  
Body Mass ◽  
Hdl Cholesterol ◽  
Fibroblast Growth Factor 21 ◽  
Control Group ◽  
Fibroblast Growth ◽  
Anthropometric Parameters ◽  
Cholesterol Levels

Abstract Introduction The goal of the study was to investigate fibroblast growth factor-21 (FGF-21) levels in acromegalic patients in relation to the disease activity and to compare them with controls. Further, we aimed to evaluate the associations between FGF-21 and random growth hormone (GH), insulin-like growth factor-1 (IGF-1), metabolic and anthropometric parameters. Materials and methods The study group consisted of 50 acromegalic patients divided into 3 subgroups on the basis of disease activity (AA – active acromegaly, CD – controlled disease, CA – cured acromegaly). 27 subjects were assigned to the control group (CG). Blood samples were obtained from all participants to assess FGF-21, GH, IGF-1, lipids, glucose and insulin levels. Body mass, body mass index and body composition were also evaluated. Results There were no statistically significant differences in FGF-21 concentrations across all groups despite of subjects classification. FGF-21 correlated positively with random GH in the groups: CA, CD+CA, AA+CD+CA (r=0.48, p=0.049; r=0.39, p=0.023; r=0.33, p=0.02; respectively); with IGF-1 in the AA+CD+CA group (r=0.29, p=0.041); with triglycerides in the following groups: CD, CD+CA, AA+CD+CA (r=0.63, p=0.08; r=0.44, p=0.01; r=0.37, p=0.007; respectively) and with age in the CG and CD+CA groups (r=0.41, p=0.029; r=0.42, p=0.029; respectively). There were statistically significant negative correlations between FGF-21 and HDL-cholesterol levels in the groups: CD, CD+CA, AA+CD+CA (r=-0.53, p=0.03; r=-0.37, p=0.032; r=-0.29, p=0.036, respectively). Conclusions FGF-21 levels were similar in patients with acromegaly compared to controls. However, our results indicate that FGF-21 may have a potential role in the development of acromegaly complications.

scholarly journals Increased Circulating and Epicardial Adipose Tissue mRNA Expression of Fibroblast Growth Factor-21 After Cardiac Surgery: Possible Role in Postoperative Inflammatory Response and Insulin Resistance

2011 ◽  
pp. 757-767 ◽  
Author(s):  
T. KOTULÁK ◽  
J. DRÁPALOVÁ ◽  
P. KOPECKÝ ◽  
Z. LACINOVÁ ◽  
P. KRAMÁŘ ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Cardiac Surgery ◽  
Growth Factor ◽  
Mrna Expression ◽  
Fibroblast Growth Factor ◽  
Serum Glucose ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Baseline Serum

We studied the changes in serum fibroblast growth factor-21 (FGF-21) concentrations, its mRNA, and protein expression in skeletal muscle and adipose tissue of 15 patients undergoing cardiac surgery. Blood samples were obtained: prior to initiation of anesthesia, prior to the start of extracorporeal circulation, upon completion of the surgery, and 6, 24, 48, and 96 hours after the end of the surgery. Tissue sampling was performed at the start and end of surgery. The mean baseline serum FGF-21 concentration was 63.1 (43.03-113.95) pg/ml and it increased during surgery with peak 6 hours after its end [385.5 (274.55-761.65) pg/ml, p<0.001], and returned to baseline value [41.4 (29.15-142.83) pg/ml] 96 hours after the end of the surgery. Serum glucose, insulin, CRP, IL-6, IL-8, MCP-1, and TNF-alpha concentrations significantly increased during the surgery. Baseline FGF-21 mRNA expression in skeletal muscle was higher than in both adipose tissue depots and it was not affected by the surgery. Epicardial fat FGF-21 mRNA increased after surgery. Muscle FGF-21 mRNA positively correlated with blood glucose levels at the end of the surgery. Our data suggest a possible role of FGF-21 in the regulation of glucose metabolism and insulin sensitivity in surgery-related stress.

scholarly journals SAT-046 Insulin-Like Growth Factor and Fibroblast Growth Factor 21 in Men with Klinefelter Syndrome

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Simon Chang ◽  
Rikke Hjortebjerg ◽  
Anders Bojesen ◽  
Mette Bjerre ◽  
Claus Hojbjerg Gravholt
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Klinefelter Syndrome ◽  
Protein A ◽  
Serum Levels ◽  
Fibroblast Growth Factor 21 ◽  
Control Group ◽  
Insulin Like Growth Factor ◽  
Fibroblast Growth ◽  
Igf System

Abstract Background: Men with 47, XXY Klinefelter syndrome (KS) commonly present with obesity, metabolic disorders, and insulin insensitivity. The insulin-like growth factor (IGF) system has pleiotropic effects including regulation of glucose metabolism. Fibroblast growth factor 21 (FGF21) is associated with weight loss and favourable metabolic changes, but patients with obesity or type 2 diabetes might be resistant to this effect despite presenting with increased levels. Aim: To describe levels of components in the IGF system and FGF21 among men with KS, either treated or not treated with testosterone supplementation therapy (TT), in comparison with control males. Methods: A total of 66 men with KS were included, 33 without current TT and 33 with current TT. A control group of 70 healthy age-matched males were included. Serum levels of insulin-like growth factor 1 (IGF-1), insulin-like growth factor-binding protein 3 (IGFBP3), pregnancy-associated plasma protein A (PAPP-A), FGF21, and fibroblast activation protein (FAP) were compared between the three groups applying the Kruskal-Wallis test. Results: Levels of (IGF-1 µg/L) were not different between the groups (median (25-75 %), untreated KS 162 (140-201.5), treated KS 165 (128.5-215), controls 176.5 (150.8-214.5), p=0.5). Similarly, FGF21 levels (ng/L) were comparable between the groups (median (25-75 %), untreated KS 84.7 (53.3-217.6), treated KS 97.2 (56.4-224.8), controls 100.3 (66.0-191.0), p=0.9). Levels of IGFBP3, PAPP-A and FAP were also found to be comparable between the groups (p≥0.2). Conclusion: This was the first study investigating FGF21 in men with KS. Our results indicate that regulation of the IGF-1 system and levels of FGF21 are not altered in men with KS compared with age-matched controls, and that TT in men with KS does not affect these systems.

scholarly journals Fibroblast Growth Factor-1 Suppresses TGF-β-Mediated Myofibroblastic Differentiation of Rat Hepatic Stellate Cells

2016 ◽  
Vol 59 (4) ◽  
pp. 124-132
Author(s):  
Eva Peterová ◽  
Lucie Podmolíková ◽  
Martina Řezáčová ◽  
Alena Mrkvicová
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Hepatic Stellate Cells ◽  
Transforming Growth Factor ◽  
Collagen Gel ◽  
Stellate Cells ◽  
Critical Event ◽  
Fibroblast Growth ◽  
Enhanced Production ◽  
Tgf Β1

Myofibroblast expansion is a critical event in the pathogenesis of liver fibrosis. The activation of hepatic stellate cells (HSC) to myofibroblast (MFB) results in the enhanced production of extracellular matrix (ECM). In this study, we explored the effect of acidic fibroblast growth factor (FGF-1) treatment on a transforming growth factor (TGF-β1) induced MFB conversion. We used HSC-T6 cell line, which represents well-established model of activated HSC. These cells strongly expressed α-smooth muscle actin (α-SMA) and fibronectin (FN-EDA) after stimulation with TGF-β1, which is a stimulus for MFB differentiation and ECM production. FGF-1 reduced proteins expression to levels comparable with untreated cells. Mild repression of secreted gelatinases was seen in culture media after FGF-1 treatment. The exposure of cells to collagen gel leads to changes in cell morphology and in expression of MFB markers. Lack of α-SMA in cells embedded to collagen gel was detected. When stimulated with TGF-β1, the cells increased expression of FN-EDA, but not α-SMA. Although the cells on plastic and in collagen gel show different properties, FGF-1 reduced expression of FN-EDA in both conditions. Disrupting TGF-β1 signalling pathway represents a potential strategy for the treatment of fibrosis. We showed that FGF-1 could antagonize signals initiated by TGF-β1.

scholarly journals Thioredoxin-1 and Correlations of the Plasma Cytokines Regarding Aortic Valve Stenosis Severity

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 1041
Author(s):  
Peteris Tretjakovs ◽  
Juris Lurins ◽  
Simons Svirskis ◽  
Gita Gersone ◽  
Dace Lurina ◽  
...  
Keyword(s):  
Growth Factor ◽  
Aortic Valve ◽  
Fibroblast Growth Factor ◽  
Aortic Valve Stenosis ◽  
Plasma Levels ◽  
Fibroblast Growth Factor 21 ◽  
Control Group ◽  
Fibroblast Growth ◽  
Local Inflammatory Response ◽  
Thioredoxin 1

Aortic valve stenosis (AS) develops not only with a pronounced local inflammatory response, but also oxidative stress is involved. The aim of this study was to evaluate the plasma levels of thioredoxin-1 (TRX1), myeloperoxidase (MPO), chemerin, growth differentiation factor 15 (GDF-15), angiopoietin-2 (Ang-2), vascular endothelial growth factor A (VEGF-A), fibroblast growth factor 2 (FGF-2), fibroblast growth factor 21 (FGF-21), and metalloproteinase (MMP)-1, -3, and -9 in acquired AS patients as well as to clarify the correlations of TXR1 and the plasma inflammatory biomarkers regarding AS severity. AS patients were classified into three groups: 16 patients with mild AS stenosis, 19 with moderate and 11 with severe AS, and 30 subjects without AS were selected as a control group. AS patients had significantly higher plasma levels of TRX1 compared to controls, but the highest difference was found in mild AS patients compared to the controls. We conclude that AS is associated with significantly increased plasma TRX1 levels, and TRX1 might serve as a specific and sensitive biomarker of AS. TRX1 and also chemerin, GDF-15, VEGF-A, FGF-2 and FGF-21 significantly correlate with AS severity degrees. TRX1 also showed positive association with FGF-2, VEGF-A, and MMP-3 in all AS patients.

scholarly journals Effect of High Concentrations of Fructose on the Expression of TGF-β and α-SMA Genes in Human Hepatic Stellate Cells

2020 ◽  
Vol 11 (3) ◽  
Author(s):  
Elham Shakerian ◽  
Hamid Yaghooti ◽  
Alireza Kheirollah ◽  
Narges Mohammadtaghvaei
Keyword(s):  
Liver Fibrosis ◽  
Mrna Expression ◽  
Liver Damage ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Control Group ◽  
Chronic Liver Damage ◽  
Fructose Intake ◽  
High Fructose ◽  
Human Hscs

Background: Liver fibrosis is a reversible response to wound-healing that occurs in most forms of chronic liver damage, beginning with the activation of hepatic stellate cells (HSCs). The increased expression of genes, such as beta-converting growth factor (TGF-β) and actin-alpha smooth muscle (α-SMA) indicates the activation of HSCs. During liver damage, HSCs are activated and converted to myofibroblasts. As a result, the expression of TGF-β and αSMA genes in HSCs increases and leads to liver fibrosis. High fructose intake is known to have harmful effects on human health. Due to the persistent increase in high fructose intake via many beverages and foods in industrialized countries, much concern has been raised about the effect of fructose on liver damage, but its role in activating human HSCs has not been studied. Objectives: We aimed to investigate the effect of high fructose concentration on human HSCs activation by measuring the level of mRNA expression of TGF-β and α-SMA genes involved in liver fibrosis. Methods: Human HSCs were cultured in Dulbecco’s Modified Eagle’s Medium (DMEM) plus 10% Fetal Bovine Serum (FBS) at 37°C in 5% CO2. Cells were incubated in media containing 25 and 30 mM fructose for 48 h. The control group was incubated in DMEM without fructose. The cells were serum-starved for 24 h before treatment. Then, the total RNA was extracted, reversely transcribed into cDNA, and underwent Quantitative Real-time PCR (qRT-PCR). Results: The results indicated that the mRNA expression of TGF-β and αSMA genes significantly increased by treating with 25 and 30 mM fructose in HSCs when compared to the control group (P < 0.05). Conclusions: The increase in the mRNA of TGF-β and αSMA genes is used as a standard marker for HSC activation, leading to liver fibrosis. The results demonstrated that high fructose concentration could activate HSCs and increase the levels of TGF-β and αSMA in these cells. Thus, controlling fructose consumption and identifying the mechanism of fructose action is important to treat and reduce liver injury.

scholarly journals Transient postprandial increase in intact circulating fibroblast growth factor-21 levels after Roux-en-Y gastric bypass: a randomized controlled clinical trial

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11174
Author(s):  
Mette S. Nielsen ◽  
Susanna Søberg ◽  
Julie B. Schmidt ◽  
Anne Chenchar ◽  
Anders Sjödin ◽  
...  
Keyword(s):  
Weight Loss ◽  
Gastric Bypass ◽  
Growth Factor ◽  
Energy Balance ◽  
Fibroblast Growth Factor ◽  
Negative Energy ◽  
Negative Energy Balance ◽  
Fibroblast Growth Factor 21 ◽  
Control Group ◽  
Fibroblast Growth

Background Despite a consistent link between obesity and increased circulating levels of fibroblast growth factor-21 (FGF21), the effect of weight-loss interventions on FGF21 is not clear. We aimed to determine the short- and long-term effects of Roux-en-Y gastric bypass (RYGB) on intact plasma FGF21 levels and to test the hypothesis that RYGB, but not diet-induced weight loss, increases fasting and postprandial responses of FGF21. Method Twenty-eight participants with obesity followed a low-calorie diet for 11 weeks. The 28 participants were randomized to undergo RYGB surgery at week 8 (RYGB group, n = 14), or to a control group scheduled for surgery at week 12 (n = 14). Fasting levels of intact, biologically active FGF21 (amino acids 1-181) and its postprandial responses to a mixed meal were assessed at week 7 and 11, and 78 weeks (18 months) after RYGB. Results At week 11 (3 weeks after RYGB), postprandial responses of intact FGF21 were enhanced in participants undergoing surgery at week 8 (change from week 7 to 11: P = 0.02), whereas no change was found in non-operated control participants in similar negative energy balance (change from week 7 to 11: P = 0.81). However, no between-group difference was found (P = 0.27 for the group-week-time interaction). Fasting, as well as postprandial responses in intact FGF21, were unchanged 18 months after RYGB when both the RYGB and control group were collapsed together (change from week 7 to 78 weeks after RYGB: P = 0.17). Conclusion Postprandial intact FGF21 levels were enhanced acutely after RYGB whereas no signs of sustained changes were found 18 months after surgery. When comparing the acute effect of RYGB with controls in similar negative energy balance, we failed to detect any significant differences between groups, probably due to the small sample size and large inter-individual variations, especially in response to surgery.

scholarly journals GCN2 is required to increase fibroblast growth factor 21 and maintain hepatic triglyceride homeostasis during asparaginase treatment

2015 ◽  
Vol 308 (4) ◽  
pp. E283-E293 ◽  
Author(s):  
Gabriel J. Wilson ◽  
Brittany A. Lennox ◽  
Pengxiang She ◽  
Emily T. Mirek ◽  
Rana J. T. Al Baghdadi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Mrna Expression ◽  
Fibroblast Growth Factor ◽  
Liver Dysfunction ◽  
Antioxidant Defenses ◽  
Initiation Factor ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Hepatic Lipid ◽  
Hepatic Expression

The antileukemic agent asparaginase triggers the amino acid response (AAR) in the liver by activating the eukaryotic initiation factor 2 (eIF2) kinase general control nonderepressible 2 (GCN2). To explore the mechanism by which AAR induction is necessary to mitigate hepatic lipid accumulation and prevent liver dysfunction during continued asparaginase treatment, wild-type and Gcn2 null mice were injected once daily with asparaginase or phosphate buffered saline for up to 14 days. Asparaginase induced mRNA expression of multiple AAR genes and greatly increased circulating concentrations of the metabolic hormone fibroblast growth factor 21 (FGF21) independent of food intake. Loss of Gcn2 precluded mRNA expression and circulating levels of FGF21 and blocked mRNA expression of multiple genes regulating lipid synthesis and metabolism including Fas, Ppara, Pparg, Acadm, and Scd1 in both liver and white adipose tissue. Furthermore, rates of triglyceride export and protein expression of apolipoproteinB-100 were significantly reduced in the livers of Gcn2 null mice treated with asparaginase, providing a mechanistic basis for the increase in hepatic lipid content. Loss of AAR-regulated antioxidant defenses in Gcn2 null livers was signified by reduced Gpx1 gene expression alongside increased lipid peroxidation. Substantial reductions in antithrombin III hepatic expression and activity in the blood of asparaginase-treated Gcn2 null mice indicated liver dysfunction. These results suggest that the ability of the liver to adapt to prolonged asparaginase treatment is influenced by GCN2-directed regulation of FGF21 and oxidative defenses, which, when lost, corresponds with maladaptive effects on lipid metabolism and hemostasis.

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