Essential Role of Lyn in Fibrosis

Citations Over TimeTop 22% of 2016 papers

Abstract

Fibrotic disorders involve replacement of normal parenchyma with myofibroblasts, which deposit connective tissue, leading to obliteration of the function of the underlying organ. The treatment options are inadequate and reflect the fact that signaling targets in myofibroblasts are unknown. Here we identify the hyperactive Lyn signaling in myofibroblasts of patients with chronic pancreatitis-induced fibrosis. Lyn activation coexpress with markers of activated myofibroblasts, and is increased ~11-fold in chronic pancreatitis compared to normal tissue. Inhibition of Lyn with siRNA or INNO-406 leads to the substantial decrease of migration and proliferation of human chronic pancreatitis myofibroblasts in vitro, while leaving migration and proliferation of normal myofibroblasts only slightly affected. Furthermore, inhibition of Lyn prevents synthesis of procollagen and collagen in myofibroblasts in a mouse model of chronic pancreatitis-induced fibrosis. We conclude that Lyn, as a positive regulator of myofibroblast migration, proliferation, and collagen production, is a key target for preventing fibrosis.

Related Papers

• → Connective Tissue Growth Factor in Indomethacin-Induced Rat Gastric Ulcer(2002)8 cited
• → Transforming Growth Factor-β (TGF-β) Expression Is Increased in the Subsynovial Connective Tissue in a Rabbit Model of Carpal Tunnel Syndrome(2014)11 cited
• The Effect of Haikunshenxi Caps on the Connective Tissue Growth Factor Protein and its mRNA’s Expression on Adriamycin-induced Nephropathicy Rats(2006)
• Significance of expression of connective tissue growth factor (CTGF) in kidney and urinary CTGF measurement in diabetic patients(2005)
• Expression of connective tissue growth factor in keratinocytes of oral submucous fibrosis(2006)