title: Significance of α-SMA in myofibroblasts emerging in renal tubulointerstitial fibrosis.
abstract: 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)-β1, but not with 10% FBS+TGF-β1. The TGF-β1-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.
authors.affiliation: Department of Molecular Anatomy, Faculty of Medicine, Oita University, Hasama-machi, Yufu, Oita, Japan. kina@oita-u.ac.jp
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ina
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kitamura
authors.forename: Shuji
authors.initials: S
authors.lastname: Tatsukawa
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Fujikura
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D020013:Calcium Signaling; D002417:Cattle; D018929:Cell Culture Techniques; D002460:Cell Line; D054338:Cell Transdifferentiation / Q000502:physiology; D003094:Collagen; D003470:Culture Media; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005355:Fibrosis; D005782:Gels; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology*; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D058628:Myofibroblasts / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000199:Actins; D003094:Collagen; D003470:Culture Media; D005782:Gels; D053773:Transforming Growth Factor beta1; C498862:Acta2 protein, rat