calpastatin and Liver-Cirrhosis

Fibrosis is a common pathologic outcome of chronic disease resulting in the replacement of normal tissue parenchyma with a collagen-rich extracellular matrix produced by myofibroblasts. Although the progenitor cell types and cellular programs giving rise to myofibroblasts through mesenchymal transition can vary between tissues and diseases, their contribution to fibrosis initiation, maintenance, and progression is thought to be pervasive. Here, we showed that the ability of transforming growth factor-β (TGFβ) to efficiently induce myofibroblast differentiation of cultured epithelial cells, endothelial cells, or quiescent fibroblasts is dependent on the induced expression and activity of dimeric calpains, a family of non-lysosomal cysteine proteases that regulate a variety of cellular events through posttranslational modification of diverse substrates. siRNA-based gene silencing demonstrated that TGFβ-induced mesenchymal transition of a murine breast epithelial cell line was dependent on induction of expression of calpain 9 (CAPN9), an isoform previously thought to be restricted to the gastrointestinal tract. Mice lacking functional CAPN9 owing to biallelic targeting of

Topics: Angiotensin II; Animals; Bleomycin; Calcium-Binding Proteins; Calpain; Carbon Tetrachloride; Cell Line; Dogs; Epithelial-Mesenchymal Transition; Fibrosis; Humans; Isoenzymes; Liver Cirrhosis; Male; Mice, Inbred C57BL; Molecular Targeted Therapy; Myocardium; Protein Biosynthesis; Protein Multimerization; RNA Stability; Signal Transduction; Transforming Growth Factor beta