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

K Ina, H Kitamura, S Tatsukawa… - … and histopathology, Vol …, 2011 - digitum.um.es
K Ina, H Kitamura, S Tatsukawa, Y Fujikura
Histology and histopathology, Vol. 26, nº 7 (2011), 2011digitum.um.es
Myofibroblast transdifferentiation plays a crucial role in the development and progression of
renal tubulointerstitial fibrosis. However, the significance of α-smooth muscle actin (α-SMA)
expression, which is the major morphological characteristic of myofibroblasts, remains to be
determined in detail. The effect of α-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)+ …
Myofibroblast transdifferentiation plays a crucial role in the development and progression of renal tubulointerstitial fibrosis. However, the significance of α-smooth muscle actin (α-SMA) expression, which is the major morphological characteristic of myofibroblasts, remains to be determined in detail. The effect of α-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 α- 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.
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