Induction of Liver-Associated Transforming Growth Factor β1 (TGF-β1) mRNA Expression by Carbon Tetrachloride Leads to the Inhibition of T Helper 2 Cell-Associated Lymphokines

1997 ◽  
Vol 144 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Young Jin Jeon ◽  
Seung Hyun Han ◽  
Kyu Hwan Yang ◽  
Norbert E. Kaminski
Author(s):  
Brinnell Annette Caszo ◽  
Azdayanti Muslim ◽  
Zanariah Awang ◽  
Effat Omar ◽  
Effendi Ibrahim ◽  
...  

ABSTRACTObjective: Elevated levels of leptin may be responsible directly for progression and severity of renal disease in obesity and hypertension. It may exertits effects by promoting fibrosis through the actions of transforming growth factor-β1 (TGF-β1) and the Smad pathway. This study determines theeffect of leptin administration on the development of renal fibrosis in nonobese spontaneously hypertensive rats (SHRs).Methods: Male SHRs, aged 12-14 weeks, were injected with either leptin (60 µg/kg/day) or saline (for the control group) subcutaneously daily for42 days. At the end of the experimental period, animals were euthanized and their kidneys were removed. The right kidney was harvested for thedetermination of messenger ribonucleic acid (mRNA) expression of TGF-β1, Smad2, Smad3, and bone morphogenic protein 7 (BMP7). The left kidneyswere stored in neutral buffered 10% formalin until they were processed and stained with hematoxylin and eosin. Prepared slides were examinedunder light microscopy. 30 consecutive glomeruli were examined for the cell counts based on the number of nuclei seen and the total area of glomeruli.Results: No significant difference was evident in renal function between control and leptin-treated rats. Cellularity and area of glomeruli were also notdifferent between the two groups. mRNA expression of TGF-β1, Smad2, and BMP7 were, however, higher in leptin-treated rats.Conclusion: It appears that 6 weeks of leptin administration increases renal TGF-β1 and Smad2 levels but with little morphological changes in thekidney. Whether the elevated BMP7 expression was responsible for lack of effect of leptin on renal morphological changes remains unclear.Keywords: Leptin, Renal function, Hypertension, Glomerulus, Transforming growth factor-β1, Smad, Spontaneously hypertensive rats.


2012 ◽  
Vol 32 (4) ◽  
pp. 462-472 ◽  
Author(s):  
Kazuo Serie ◽  
Noboru Fukuda ◽  
Shigeki Nakai ◽  
Hiroyuki Matsuda ◽  
Takashi Maruyama ◽  
...  

ObjectiveEncapsulating peritoneal sclerosis (EPS) is a devastating fibrotic complication in patients treated with peritoneal dialysis (PD). Transforming growth factor β1 (TGF-β1) is a pivotal factor in the induction of EPS.MethodsTo develop pyrrole-imidazole (PI) polyamide, a novel gene silencer, targeted to the TGF-β1 promoter (Polyamide) for EPS, we examined the effects of Polyamide on messenger RNA (mRNA) expression of TGF-β 1, vascular endothelial growth factor (VEGF), and extracellular matrix (ECM) in mesothelial cells in vitro, and on the thickness of injured peritoneum evaluated by histology and high- resolution regional elasticity mapping in rats in vivo.ResultsPolyamide significantly lowered mRNA expression of TGF-β 1 and ECM in vitro. Polyamide labeled with fluorescein isothiocyanate was taken up into the injured peritoneum and was strongly localized in the nuclei of most cells. Polyamide 1 mg was injected intraperitoneally 1 or 3 times in rats receiving a daily intraperitoneal injection of chlorhexidine gluconate and ethanol (CHX) for 14 days. Polyamide significantly suppressed peritoneal thickening and the abundance of TGF-β 1 and fibronectin mRNA, but did not affect expression of VEGF mRNA in the injured peritoneum. Elasticity distribution mapping showed that average elasticity was significantly lower in Polyamide-treated rats than in rats treated solely with CHX.ConclusionsPolyamide suppressed the stiffness, ECM formation, and thickening of the injured peritoneum that occurs during EPS pathogenesis. These data suggest that PI polyamide targeted to the TGF-β 1 promoter will be a specific and feasible therapeutic strategy for patients with EPS.


1998 ◽  
Vol 275 (3) ◽  
pp. F458-F466 ◽  
Author(s):  
Anne-Christine Poncelet ◽  
H. William Schnaper

Transforming growth factor (TGF)-β1 has been implicated in glomerular extracellular matrix accumulation. Since the spectrum and mechanism of changes in collagen turnover have not been fully characterized, we evaluated effects of TGF-β1 on collagen expression by human mesangial cells. TGF-β1 induced increased α1(I), α1(III), and α1(IV) collagen mRNA expression. Greater mRNA expression of matrix metalloproteinase (MMP)-2 was compensated by increased tissue inhibitor of metalloproteinases (TIMP)-2 mRNA. There was no change in TIMP-1 or membrane-type MMP mRNA expression, whereas MMP-1 mRNA decreased. Types I and IV collagen protein accumulated in both the cell layer and medium. Changes in collagen mRNA and protein occurred within 4 and 8 h, respectively. MMP-2 and TIMP-1 and -2 activities showed little change. Cycloheximide markedly decreased collagen detection within 4 h and reversed late, but not early, changes in α1(I) collagen mRNA. In this system, increased synthesis may be more significant than degradation for collagen accumulation, but collagen is short-lived in culture. Diverse TGF-β1 actions on collagen turnover may be either immediate or mediated through synthesis of regulatory molecules.


2016 ◽  
Vol 291 (25) ◽  
pp. 13160-13174 ◽  
Author(s):  
Simeng Chen ◽  
Teng Feng ◽  
Maja Vujić Spasić ◽  
Sandro Altamura ◽  
Katja Breitkopf-Heinlein ◽  
...  

2018 ◽  
Vol 4 (3) ◽  
pp. 50-56
Author(s):  
Vikram V Nimbalkar ◽  
Ravina P Shelke ◽  
Urmila E Kadu ◽  
Pandurang M Gaikwad

Background: Activation of hepatic stellate cells (HSC) plays central role in the development of liver fibrosis. In HSC activation, the transforming growth factor-β1 (TGF-β1) is considered to be the main stimuli factor. Diosgenin are the steroidal saponin and found in Trigonella foenum graecum Linn (Fenugreek) and some other species of Dioscorea. Diosgenin attenuates HSC activation by inhibiting transforming growth factor-β. Aim: In present study an attempt was made to explore the effect of diosgenin on liver fibrosis. Methods: Liver fibrosis was induced in rats by carbon tetrachloride (CCl4) 1 ml/kg intraperitoneally twice a week for 28 days and cisplatin 3mg/kg intraperitoneally at 0, 1, 3 week for 4 weeks. The extent of liver fibrosis was assessed by measuring the weight of liver and levels of total bilirubin (TBL), hydroxyproline (HP) and serum enzymes due to deposition of extracellular matrix (ECM). Results: The administration of diosgenin reduced the liver weight of CCl4 and cisplatin treated animals and reduced the TBL, HP level and serum enzymes significantly and inhibited liver fibrosis induced by CCl4 and cisplatin. Conclusion: The result obtained in the present investigation, Diosgenin treatment exerted significant hepatoprotective effect in animals by inhibiting ECM deposition and HSCs activation. 


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