Significance of ?-SMA in myofibroblasts emerging in renal tubulointerstitial fibrosis

• Autores: Keisuke Ina, Hirokazu Kitamura, Shuji Tatsukawa, Yoshihisa Fujikura
• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 26, Nº. 7, 2011, págs. 855-866
• Idioma: inglés
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• Resumen

  • Myofibroblast transdifferentiation plays a crucial role in the development and progression of renal tubulointerstitial fibrosis. However, the significance of a-smooth muscle actin (?-SMA) expression, which is the major morphological characteristic of myofibroblasts, remains to be determined in detail. The effect of ?-SMA expression on fibrosis tissue was examined by using a fibrosis model (collagen gel) in vitro. The transdifferentiation of fibroblasts into myofibroblasts was triggered in the culture medium with 0.5% fetal bovine serum (FBS)+transforming growth factor (TGF)-ß1, but not with 10% FBS+TGF-ß1. The TGF-ß1-induced gel contraction caused by myofibroblasts was greater than that by fibroblasts. Gel contraction by myofibroblasts involved the Ca2+-dependent myosin light chain kinase pathway, as well as the activation of Rho kinase and p38 mitogen-activated protein kinase (MAPK). Taken together, these findings suggest that ?-SMA expression in renal interstitial fibroblasts, i.e., myofibroblast transdifferentiation, accelerates the contraction of the tubulointerstitial fibrosis tissue via the Ca2+-dependent pathway, in addition to the pathways involved in fibroblast contraction; this event may lead to renal atrophy and renal failure.