Matrix protein synthesis by glomerular mesangial cells in culture: Effects of transforming growth factor β (TGFβ) and platelet-derived growth factor (PDGF) on fibronectin and collagen type IV mRNA

1995 ◽  
Vol 163 (3) ◽  
pp. 451-457 ◽  
Author(s):  
Gertrud Maria Hänsch ◽  
Christof Wagner ◽  
Antje Bürger ◽  
Wenjie Dong ◽  
G. Staehler ◽  
...  
Keyword(s):  
Growth Factor ◽  
Matrix Protein ◽  
Collagen Type ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Transforming Growth Factor Β ◽  
Collagen Type Iv ◽  
Glomerular Mesangial Cells ◽  
Type Iv ◽  
Culture Effects

Effect of Simvastatin on Expression of Transforming Growth Factor-β and Collagen Type IV in Rat Mesangial Cells

Pharmacology ◽  
2011 ◽  
Vol 88 (3-4) ◽  
pp. 188-192 ◽  
Author(s):  
Yan-Bo Li ◽  
Jia-Jing Yin ◽  
Hong-Jie Wang ◽  
Jun Wang ◽  
Hui Tian ◽  
...  
Keyword(s):  
Growth Factor ◽  
Collagen Type ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Transforming Growth Factor Β ◽  
Collagen Type Iv ◽  
Type Iv

scholarly journals C-peptide prevents SMAD3 binding to alpha promoters to inhibit collagen type IV synthesis

2018 ◽  
Vol 61 (1) ◽  
pp. 47-56 ◽  
Author(s):  
Yanning Li ◽  
Yan Zhong ◽  
Wenjian Gong ◽  
Xuehan Gao ◽  
Huanli Qi ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Protein Content ◽  
Collagen Type ◽  
Transforming Growth Factor ◽  
Nuclear Translocation ◽  
Mesangial Cells ◽  
Collagen Type Iv ◽  
Pathological Changes ◽  
C Peptide ◽  
Type Iv

Activation of transforming growth factor β1 (TGFB1)/SMAD3 signaling may lead to additional synthesis of collagen type IV (COL4), which is a major contributor to extracellular matrix (ECM) accumulation in diabetic nephropathy (DN). C-peptide can attenuate fibrosis to have unique beneficial effects in DN. However, whether and how C-peptide affects TGFB1/SMAD3-activated COL4 synthesis is unclear. In this study, pathological changes, expression of COL4 a1-a5 chains (Col4a1-a5), COL4 distribution and protein and TGFB1 and SMAD3 protein were first assessed in a rat model of diabetes. Then, rat mesangial cells were treated with high glucose (HG) and/or C-peptide to investigate the underlying mechanism.Col4a1-a5expression, COL4 protein and secretion, TGFB1 protein, SMAD3 nuclear translocation and binding of SMAD3 to its cognate sites in the promoters ofCol4a1a2,Col4a3a4andCol4a5were measured. It was found that C-peptide attenuated glomerular pathological changes and suppressed renalCol4a1-a5mRNA expression, COL4 protein content and TGFB1 protein content. C-peptide had a dose-dependent effect to inhibitCol4a1-a5mRNA expression, COL4 protein content and secretion, in HG-stimulated mesangial cells. In addition, the HG-induced increase in TGFB1 protein content was significantly reduced by C-peptide. Although not apparently affecting SMAD3 nuclear translocation, C-peptide prevented SMAD3 from binding to its sites in theCol4a1a2,Col4a3a4andCol4a5promoters in HG-stimulated mesangial cells. In conclusion, C-peptide could prevent SMAD3 from binding to its sites in theCol4a1a2,Col4a3a4andCol4a5promoters, to inhibit COL4 generation. These results may provide a mechanism for the alleviation of fibrosis in DN by C-peptide.

BMP7 antagonizes TGF-β-dependent fibrogenesis in mesangial cells

2003 ◽  
Vol 284 (5) ◽  
pp. F1006-F1013 ◽  
Author(s):  
Shinong Wang ◽  
Raimund Hirschberg
Keyword(s):  
Growth Factor ◽  
Collagen Type ◽  
Mesangial Cells ◽  
Tissue Growth ◽  
Luciferase Reporter ◽  
Renal Diseases ◽  
Collagen Type Iv ◽  
Mrna Levels ◽  
Type Iv ◽  
Pai 1

Exogenous administration of recombinant human bone morphogenetic protein (BMP)-7 was recently shown to ameliorate renal glomerular and interstitial fibrosis in rodents with experimental renal diseases. We tested the hypothesis that BMP7 functions by antagonizing profibrogenic events that are induced by transforming growth factor (TGF)-β in cultured mesangial cells. Incubation of murine mesangial cells with TGF-β (50–200 pM) increased cell-associated collagen type IV and fibronectin, soluble collagen type IV, thrombospondin, and connective tissue growth factor (CTGF). Coincubation with recombinant human BMP7 (200 pM) reduced the increase of these ECM proteins and CTGF. The changes in collagen type IV and fibronectin proteins occurred without concomitant changes in collagen type α1IV and fibronectin mRNA levels, suggesting that TGF-β and BMP7 act primarily by affecting ECM protein degradation. Indeed, TGF-β decreases the levels and activity of matrix metalloprotease (MMP)-2, the major metalloprotease that is secreted by mesangial cells. Moreover, BMP7 inhibits TGF-β-induced activation of MMP2. Because TGF-β reduces the activity of MMPs through increasing plasminogen activator inhibitor (PAI)-1, we tested whether BMP7 interferes with this TGF-β effect. BMP7 reduces, by about two-thirds, the activation of a PAI-1 promoter/luciferase reporter in cells stably transfected with this construct. The findings from these studies indicate that BMP7 reduces TGF-β-induced ECM protein accumulation in cultured mesangial cells primarily by maintaining levels and activity of MMP2 partially through prevention of TGF-β-dependent upregulation of PAI-1.

scholarly journals Repression of let-7 by transforming growth factor-β1-induced Lin28 upregulates collagen expression in glomerular mesangial cells under diabetic conditions

2014 ◽  
Vol 307 (12) ◽  
pp. F1390-F1403 ◽  
Author(s):  
Jung Tak Park ◽  
Mitsuo Kato ◽  
Linda Lanting ◽  
Nancy Castro ◽  
Bo Young Nam ◽  
...  
Keyword(s):  
Growth Factor ◽  
Untranslated Region ◽  
Collagen Type ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Ectopic Expression ◽  
Transforming Growth Factor Β1 ◽  
Negative Regulator ◽  
Glomerular Mesangial Cells

Accumulation of mesangial extracellular matrix (ECM) proteins such as collagen type 1-α2 (Col1a2) and collagen type 4-α1 (Col4a1) is a key feature of diabetic nephropathy (DN). Transforming growth factor (TGF)-β1 plays important roles in ECM accumulation in DN, and evidence shows a mediatory role for microRNAs. In the present study, we found that microRNA let-7 family members (let-7b/c/d/g/i) were downregulated in TGF-β-treated mouse mesangial cells (MMCs) along with upregulation of Col1a2 and Col4a1. Ectopic expression of let-7b in TGF-β-treated MMCs attenuated Col1a2 and Col4a1 upregulation. Conversely, let-7b inhibitors increased Col1a2 and Col4a1 levels. Cotransfection of MMCs with mouse Col1a2 or Col4a1 3′-untranslated region luciferase constructs and let-7b inhibitors increased luciferase activity. However, constructs with let-7 target site mutations were unresponsive to TGF-β. TGF-β-induced 3′-untranslated region activity was attenuated by let-7b mimics, suggesting that Col1a2 and Col4a1 are direct targets of let-7b. In addition, Lin28b, a negative regulator of let-7 biogenesis, was upregulated in TGF-β-treated MMCs. Luciferase assays showed that the Lin28b promoter containing the Smad-binding element (SBE) responded to TGF-β, which was abolished in constructs without SBE. Chromatin immunoprecipitation assays showed TGF-β-induced enrichment of Smad2/3 at the Lin28b promoter, together suggesting that Lin28b is transcriptionally induced by TGF-β through SBE. Furthermore, let-7b levels were decreased, whereas Lin28b, Col1a2, and Col4a1 levels were increased, in glomeruli of diabetic mice compared with nondiabetic control mice, demonstrating the in vivo relevance of this Lin28/let-7/collagen axis. These results identify Lin28 as a new TGF-β target gene and suggest a novel role for the Lin28/let-7 pathway in controlling TGF-β-induced collagen accumulation in DN.

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