Regulation of human mesangial cell collagen expression by transforming growth factor-β1

1998 ◽  
Vol 275 (3) ◽  
pp. F458-F466 ◽  
Author(s):  
Anne-Christine Poncelet ◽  
H. William Schnaper
Keyword(s):  
Growth Factor ◽  
Mrna Expression ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Transforming Growth Factor Β1 ◽  
Collagen Turnover ◽  
Collagen Mrna ◽  
Collagen Expression ◽  
Membrane Type ◽  
Tgf Β1

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.

Connective tissue growth factor antagonizes transforming growth factor-β1/Smad signalling in renal mesangial cells

2011 ◽  
Vol 441 (1) ◽  
pp. 499-510 ◽  
Author(s):  
Helen C. O'Donovan ◽  
Fionnuala Hickey ◽  
Derek P. Brazil ◽  
David H. Kavanagh ◽  
Noelynn Oliver ◽  
...  
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Transforming Growth Factor Β1 ◽  
Tissue Growth ◽  
Transcriptional Responses ◽  
Cell Contractility ◽  
Tgf Β1

The critical involvement of TGF-β1 (transforming growth factor-β1) in DN (diabetic nephropathy) is well established. However, the role of CTGF (connective tissue growth factor) in regulating the complex interplay of TGF-β1 signalling networks is poorly understood. The purpose of the present study was to investigate co-operative signalling between CTGF and TGF-β1 and its physiological significance. CTGF was determined to bind directly to the TβRIII (TGF-β type III receptor) and antagonize TGF-β1-induced Smad phosphorylation and transcriptional responses via its N-terminal half. Furthermore, TGF-β1 binding to its receptor was inhibited by CTGF. A consequent shift towards non-canonical TGF-β1 signalling and expression of a unique profile of differentially regulated genes was observed in CTGF/TGF-β1-treated mesangial cells. Decreased levels of Smad2/3 phosphorylation were evident in STZ (streptozotocin)-induced diabetic mice, concomitant with increased levels of CTGF. Knockdown of TβRIII restored TGF-β1-mediated Smad signalling and cell contractility, suggesting that TβRIII is key for CTGF-mediated regulation of TGF-β1. Comparison of gene expression profiles from CTGF/TGF-β1-treated mesangial cells and human renal biopsy material with histological diagnosis of DN revealed significant correlation among gene clusters. In summary, mesangial cell responses to TGF-β1 are regulated by cross-talk with CTGF, emphasizing the potential utility of targeting CTGF in DN.

scholarly journals THE EFFECTS OF LEPTIN ADMINISTRATION ON RENAL FUNCTION IN SPONTANEOUSLY HYPERTENSIVE RATS

2016 ◽  
Vol 10 (1) ◽  
pp. 108
Author(s):  
Brinnell Annette Caszo ◽  
Azdayanti Muslim ◽  
Zanariah Awang ◽  
Effat Omar ◽  
Effendi Ibrahim ◽  
...  
Keyword(s):  
Renal Function ◽  
Growth Factor ◽  
Mrna Expression ◽  
Spontaneously Hypertensive Rats ◽  
Transforming Growth Factor ◽  
Morphological Changes ◽  
Transforming Growth Factor Β1 ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Tgf Β1

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.

scholarly journals Pyrrole-Imidazole Polyamide Targeting Transforming Growth Factor β1 Ameliorates Encapsulating Peritoneal Sclerosis

2012 ◽  
Vol 32 (4) ◽  
pp. 462-472 ◽  
Author(s):  
Kazuo Serie ◽  
Noboru Fukuda ◽  
Shigeki Nakai ◽  
Hiroyuki Matsuda ◽  
Takashi Maruyama ◽  
...  
Keyword(s):  
Growth Factor ◽  
Mrna Expression ◽  
Messenger Rna ◽  
Transforming Growth Factor ◽  
Fluorescein Isothiocyanate ◽  
Transforming Growth Factor Β1 ◽  
Vegf Mrna ◽  
Tgf Β1

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.

scholarly journals Transforming Growth Factor β1 (TGF-β1) Activates Hepcidin mRNA Expression in Hepatocytes

2016 ◽  
Vol 291 (25) ◽  
pp. 13160-13174 ◽  
Author(s):  
Simeng Chen ◽  
Teng Feng ◽  
Maja Vujić Spasić ◽  
Sandro Altamura ◽  
Katja Breitkopf-Heinlein ◽  
...  
Keyword(s):  
Growth Factor ◽  
Mrna Expression ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Hepcidin Mrna ◽  
Tgf Β1
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