Smooth muscle α-actin deficiency in myofibroblasts leads to enhanced renal tissue fibrosis

Myofibroblasts are a major source of proinflammatory cytokines and extracellular matrix in progressive tissue fibrosis leading to chronic organ failure. Myofibroblasts are characterized by de novo expression of smooth muscle alpha-actin (SM alpha A), which correlates with the extent of disease progression, although their exact role is unknown. In vitro cultured myofibroblasts from kidney of SM alpha A knock-out mice demonstrate significantly more prominent cell motility, proliferation, and type-I procollagen expression than those of wild-type myofibroblasts. These pro-fibrotic properties are suppressed by adenovirus-mediated SM alpha A re-expression, accompanied by down-regulation of focal adhesion proteins. In interstitial fibrosis model, tissue fibrosis area, proliferating interstitial cell number, and type-I procollagen expression are enhanced under SM alpha A deficiency. In mesangioproliferative glomerulonephritis model, cell proliferation in the mesangial area is also enhanced in SM alpha A knock-out mice. Adenoviral SM alpha A introduction into renal interstitium obviously ameliorates tissue fibrosis in interstitial fibrosis model. These results indicate that SM alpha A suppresses the pro-fibrotic properties of myofibroblasts, highlighting the significance of smooth muscle-related proteins in moderating chronic organ fibrosis under pathological conditions.