Transforming growth factor-beta 1 stimulates collagen matrix remodeling through increased adhesive and contractive potential by human renal fibroblasts
2004 | conference paper. A publication with affiliation to the University of Göttingen.
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Transforming growth factor-beta 1 stimulates collagen matrix remodeling through increased adhesive and contractive potential by human renal fibroblasts
Kondo, S.; Kagami, S.; Urushihara, M.; Kitamura, A.; Shimizu, M.; Strutz, F. M. & Mueller, G. A. et al. (2004)
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1693(2) pp. 91-100. 33rd Annual Meeting of the American-Society-of-Nephrology, TORONTO, CANADA.
Amsterdam: Elsevier Science Bv. DOI: https://doi.org/10.1016/j.bbamcr.2004.05.005
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- Authors
- Kondo, S.; Kagami, S.; Urushihara, M.; Kitamura, A.; Shimizu, M.; Strutz, Frank M.; Mueller, Gerhard A. ; Kuroda, Y.
- Abstract
- Renal tubulointerstitial fibrosis is the common final pathway leading to end-stage renal failure. Tubulointerstitial fibrosis is characterized by fibroblast proliferation and excessive matrix accumulation. Transforming growth factor-beta1 (TGF-beta1) has been implicated in the development of renal fibrosis accompanied by alpha-smooth muscle actin (alpha-SMA) expression in renal fibroblasts. To investigate the molecular and cellular mechanisms involved in tubulointerstitial fibrosis, we examined the effect of TGF-beta1 on collagen type I (collagen) gel contraction, an in vitro model of scar collagen remodeling. TGF-beta1 enhanced collagen gel contraction by human renal fibroblasts in a doseand time-dependent manner. Function-blocking anti-alpha1 or anti-alpha2 integrin subunit antibodies significantly suppressed TGF-beta1 -stimulated collagen gel contraction. Scanning electron microscopy showed that TGF-beta1 enhanced the formation of the collagen fibrils by cell attachment to collagen via alpha1beta1 and alpha2beta1 integrins. Flow cytometry and cell adhesion analyses revealed that the stimulation of renal fibroblasts with TGF-beta1 enhanced cell adhesion to collagen via the increased expression of alpha1 and alpha2 integrin subunits within collagen gels. Fibroblast migration to collagen was not up-regulated by TGF-beta1. Furthermore, TGF-beta1 increased the expression of a putative contractile protein, alpha-SNIA, by human renal fibroblasts in collagen gels. These results suggest that TGF-beta1 stimulates fibroblast- collagen matrix remodeling by increasing both integrin-mediated cell attachment to collagen and alpha-SMA expression, thereby contributing to pathological tubulointerstitial collagen matrix reorganization in renal fibrosis. (C) 2004 Elsevier B.V. All rights reserved.
- Issue Date
- 2004
- Status
- published
- Publisher
- Elsevier Science Bv
- Journal
- Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
- Conference
- 33rd Annual Meeting of the American-Society-of-Nephrology
- Conference Place
- TORONTO, CANADA
- ISSN
- 0167-4889