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

Abstract

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 (SMalphaA), which correlates with the extent of disease progression, although their exact role is unknown. In vitro cultured myofibroblasts from kidney of SMalphaA 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 SMalphaA 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 SMalphaA deficiency. In mesangioproliferative glomerulonephritis model, cell proliferation in the mesangial area is also enhanced in SMalphaA knock-out mice. Adenoviral SMalphaA introduction into renal interstitium obviously ameliorates tissue fibrosis in interstitial fibrosis model. These results indicate that SMalphaA suppresses the pro-fibrotic properties of myofibroblasts, highlighting the significance of smooth muscle-related proteins in moderating chronic organ fibrosis under pathological conditions.

• Authors: Masanobu Takeji, Toshiki Moriyama, Susumu Oseto, Noritaka Kawada, Masatsugu Hori, Enyu Imai, Takeshi Miwa
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 281 Issue 52 Pg. 40193-200 (Dec 29 2006) ISSN: 0021-9258 [Print] United States
• PMID: 17090535 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins

Topics

• Actins (biosynthesis, deficiency, genetics)
• Animals
• Cell Proliferation
• Cells, Cultured
• Disease Models, Animal
• Fibroblasts (metabolism, pathology)
• Fibrosis
• Gene Expression Regulation (genetics)
• Kidney (metabolism, pathology)
• Male
• Mesangial Cells (metabolism, pathology)
• Mice
• Mice, Knockout
• Muscle, Smooth, Vascular (metabolism, pathology)
• Nephritis, Interstitial (genetics, metabolism, pathology)
• Ureteral Obstruction (genetics, metabolism, pathology)