Sublytic complement C5b-9 complexes induce thrombospondin-1 production in rat glomerular mesangial cells via PI3-k/Akt: Association with activation of latent transforming growth factor-beta1

2007 ◽  
Vol 44 (1-3) ◽  
pp. 174
Author(s):  
Lingjuan Gao ◽  
Wen Qiu ◽  
Yingwei Wang ◽  
Wenhuan Xu ◽  
Juan Xu ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Glomerular Mesangial Cells ◽  
Transforming Growth Factor Beta1 ◽  
Thrombospondin 1

scholarly journals Elevated level of ambient glucose stimulates the synthesis of high-molecular-weight hyaluronic acid by human mesangial cells. The involvement of transforming growth factor beta1 and its activation by thrombospondin-1.

2006 ◽  
Vol 53 (2) ◽  
pp. 383-393 ◽  
Author(s):  
Natalia Yu Yevdokimova
Keyword(s):  
Molecular Weight ◽  
Growth Factor ◽  
High Molecular Weight ◽  
High Glucose ◽  
Structural Integrity ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Lower Molecular Weight ◽  
Transforming Growth Factor Beta1 ◽  
Thrombospondin 1

The dysregulation of the metabolism of glycosaminoglycan and protein components of extracellular matrix (ECM) is a typical feature of diabetic complications. High glucose-induced enrichment of ECM with hyaluronan (HA) not only affects tissue structural integrity, but influences cell metabolic response due to the variety of effects depending on the HA polymer molecular weight. TSP-1-dependent activation of TGFbeta1 axis is known to mediate numerous matrix disorders in diabetes, but its role concerning HA has not been studied so far. In this work we demonstrated that 30 mM D-glucose increased the incorporation of [(3)H]glucosamine in high-molecular-weight (> 2000 kDa) HA of medium and matrix compartments of human mesangial cultures. Simultaneously, the synthesis of HA with lower molecular weight and HA degradation were not altered. The cause of the increased high-molecular-weight HA synthesis consisted in the up-regulation of hyaluronan synthase (HAS) 2 mRNA without alterations of the expression of HAS3, which generates HA of lower molecular weight. D-Glucose at 30 mM also stimulated the production of transforming growth factor beta1 (TGFbeta1), the excessive activation of which was determined by the up-regulation of thrombospondin-1 (TSP-1). The blockage of TGFbeta1 action either by neutralizing anti-TGFbeta1 antibodies or by quenching the TGFbeta1 activation (with TSP-1-derived synthetic GGWSHW peptide) abolished the effect of high glucose on HAS2 mRNA expression and normalized the synthesis of HA. Exogenous human TGFbeta1 had the same effect on HAS2 expression and HA synthesis as high glucose treatment. Therefore, we supposed that TSP-1-dependent TGFbeta1 activation is involved in the observed high glucose effect on HA metabolism. Since high-molecular-weight HA polymers, unlike middle- and low-molecular weight HA oligosaccharides, are known to possess anti-inflammatory and anti-fibrotic functions, we suppose that the enrichment of mesangial matrix with high-molecular-weight HA may represent an endogenous mechanism to limit renal injury in diabetes.

Influence of transforming growth factor beta1 (TGF-beta1) on the behaviour of porcine thyroid epithelial cells in primary culture through thrombospondin-1 synthesis

1999 ◽  
Vol 112 (9) ◽  
pp. 1405-1416
Author(s):  
D. Claisse ◽  
I. Martiny ◽  
B. Chaqour ◽  
Y. Wegrowski ◽  
E. Petitfrere ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Follicle Cells ◽  
Dependent Manner ◽  
Transforming Growth Factor Beta1 ◽  
Thyroid Cells ◽  
Amino Terminal ◽  
Thrombospondin 1 ◽  
Inhibitor Of Protein Synthesis

Transforming growth factor beta1 (TGF-beta1) is a secreted polypeptide that is thought to play a major role in the regulation of folliculogenesis and differentiation of thyroid cells. On porcine thyroid follicular cells cultured on plastic substratum, TGF-beta1, in a concentration-dependent way, promoted the disruption of follicles, cell spreading, migration and confluency by a mechanism that did not involve cell proliferation. TGF-beta1 strongly activated the production of thrombospondin-1 and (alpha)vbeta3 integrin in a concentration-dependent manner whereas the expression of thyroglobulin was unaffected. Anisomycin, an inhibitor of protein synthesis, inhibited the effect of TGF-beta1 on cell organization. Thrombospondin-1 reproduced the effect of TGF-beta1. In the presence of thrombospondin-1 cells did not organize in follicle-like structures but, in contrast, spreaded and reached confluency independently of cell proliferation. This effect is suppressed by an RGD-containing peptide. The adhesive properties of thrombospondin-1 for thyroid cells were shown to be mediated by both the amino-terminal heparin-binding domain and the RGD domain of thrombospondin-1. Adhesion was shown to involve (alpha)vbeta3 integrin. The results show that TGF-beta1 exerted an influence upon function and behaviour of follicle cells partly mediated by the synthesis of thrombospondin-1 and of its receptor (alpha)vbeta3 integrin.

scholarly journals Transforming growth factor beta regulates cyclooxygenase-2 in glomerular mesangial cells

2006 ◽  
Vol 69 (9) ◽  
pp. 1578-1585 ◽  
Author(s):  
P. Harding ◽  
L. Balasubramanian ◽  
J. Swegan ◽  
A. Stevens ◽  
W.F. Glass
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Cyclooxygenase 2 ◽  
Glomerular Mesangial Cells ◽  
Growth Factor Beta

Suppressions of chronic glomerular injuries and TGF-β1 production by HGF in attenuation of murine diabetic nephropathy

2004 ◽  
Vol 286 (1) ◽  
pp. F134-F143 ◽  
Author(s):  
Shinya Mizuno ◽  
Toshikazu Nakamura
Keyword(s):  
Diabetic Nephropathy ◽  
Growth Factor ◽  
Renal Dysfunction ◽  
Transforming Growth Factor ◽  
Mesangial Cells ◽  
Renal Diseases ◽  
Glomerular Mesangial Cells ◽  
Diabetic Mice

Diabetic nephropathy is now the leading cause of end-stage renal diseases, and glomerular sclerotic injury is an initial event that provokes renal dysfunction during processes of diabetes-linked kidney disease. Growing evidence shows that transforming growth factor-β1 (TGF-β1) plays a key role in this process, especially in eliciting hypertrophy and matrix overaccumulation. Thus it is important to find a ligand system to antagonize the TGF-β1-mediated pathogenesis under high-glucose conditions. Herein, we provide evidence that hepatocyte growth factor (HGF) targets mesangial cells, suppresses TGF-β1 production, and minimizes glomerular sclerotic changes, using streptozotocin-induced diabetic mice. In our murine model, glomerular sclerogenesis (such as tuft area expansion and collagen deposition) progressed between 6 and 10 wk after the induction of hyperglycemia, during a natural course of diabetic disease. Glomerular HGF expression levels in the diabetic kidney transiently increased but then declined below a basal level, with manifestation of glomerular sclerogenesis. When anti-HGF IgG was injected into mice for 2 wk (i.e., from weeks 4 to 6 after onset of hyperglycemia), these glomerular changes were significantly aggravated. When recombinant HGF was injected into the mice for 4 wk (i.e., between 6 and 10 wk following streptozotocin treatment), the progression of glomerular hypertrophy and sclerosis was almost completely inhibited, even though glucose levels remained unchanged (>500 mg/dl). Even more important, HGF repressed TGF-β1 production in glomerular mesangial cells even under hyperglycemic conditions both in vitro and in vivo. Consequently, not only albuminuria but also tubulointerstitial fibrogenesis were attenuated by HGF. Overall, HGF therapy inhibited the onset of renal dysfunction in the diabetic mice. On the basis of these findings, we wish to emphasize that HGF plays physiological and therapeutic roles in blocking renal fibrogenesis during a course of diabetic nephropathy.

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