C-Abl Silencing Reduced the Inhibitory Effects of Tgf-Β1 on Apoptosis in Systemic Sclerosis Dermal Fibroblasts Publisher Pubmed



Karimizadeh E¹ ; Gharibdoost F² ; Motamed N¹ ; Jafarinejadfarsangi S¹ ; Jamshidi A² ; Mahmoudi M² Show Affiliations
Source: Molecular and Cellular Biochemistry Published:2015

Abstract

It is generally accepted that the apoptosis of myofibroblasts is a crucial event in the normal wound healing. Delay in myofibroblasts apoptosis results in fibrotic diseases such as systemic sclerosis (SSc). Transforming growth factor-β1 (TGF-β1) is an important cytokine to induce fibroblasts differentiation into myofibroblasts. Cellular Abelson (c-Abl) is known as a TGF-β1-modulating molecule in fibrosis. The role of c-Abl, TGF-β1, and their interaction in SSc myofibroblasts apoptosis has not yet been fully explored. The aim of this study was to evaluate whether TGF-β1 and inhibition of c-Abl influence Bax to Bcl-2 ratio and apoptosis in SSc and healthy dermal fibroblasts. We also would like to know whether there is interaction between TGF-β1 and c-Abl in connection with fibroblasts apoptosis or not. Bax to Bcl-2 ratio was determined using quantitative real-time polymerase chain reaction and immunoblotting. Apoptosis was detected using annexin V and nuclear staining with Hoechst dye. Our results demonstrated that inhibition of c-Abl increased SSc and healthy dermal fibroblasts susceptibility to apoptosis through increasing in Bax to Bcl-2 mRNA and protein ratios, whereas TGF-β1 promoted healthy fibroblasts resistance to apoptosis via decreasing Bax to Bcl-2 mRNA and protein ratios. In addition, c-Abl silencing reduced the effects of TGF-β1 on Bax to Bcl-2 mRNA and protein ratios. These results suggested that TGF-β1 and c-Abl individually may prevent the deletion of myofibroblasts from wounds and result in fibrosis. Results also proposed that silencing of c-Abl may promote myofibroblasts elimination from wound lesions through reduction in the TGF-β1 inhibitory effects on apoptosis. © 2015, Springer Science+Business Media New York.