The Pathological Transduction Signaling Regulates The Differentiation Of Cardiac Fibroblasts In Polymeized Collagen Matrices In Ischemic Cardiac Fibrosis

Objective To show that myofibroblast differentiation is regulated by polymerized collagen in vitro and to identify a potential mechanism by which this occurs.Methods we approach polymerized collagen to culture cardiac fibroblast from mice to mimic a model of pathological ECM in vivo. Morphology changes and growth curve of cardiac fibroblasts were observed , Expression ofβ-1 integrin,Caveolin-1, PTEN,p-Akt Ser473 and p-p44/42 MAPK(ERK1/2) was measured by western blot. Confocal microscopic immunofluorescent analysis of caveolin-1 and PTEN expression in Caveolin-1 null fibroblast reconstituted with Caveolin-1. Results We found that normal cardiac fibroblasts were able to differentiate into myofibroblast when they were cultured in polymerized collagen, meanwhile , we observed that Caveolin-1,β1-integrin and PTEN expression was decreased in the fibroblast in response to polymerized collagen. Consistent with, phosphorylation of Akt was elevated as a function of time. We also found that phosphorylation of p44/42 MAPK (Erk1/2) were increased in the fibroblasts in response to polymerized collagen. Immunofluorescence studies were performed on caveolin-1–null and wild-type fibroblasts and PTEN expression is low in Cacveolin-1 null fibroblasts.Conclusions These results indicated that the fibroblasts might be induced to myofibroblast via pathologic ECM remolding , which was affected by PTEN-PI3K/Akt or p42/44MAPK signaling pathway regulated by Caveolin-1.