title: c-Abl silencing reduced the inhibitory effects of TGF-β1 on apoptosis in systemic sclerosis dermal fibroblasts.
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.
authors: Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, P.O. Box 141556455, Tehran, Iran.
authors: Elham
authors: E
authors: Karimizadeh
authors: Farhad
authors: F
authors: Gharibdoost
authors: Nasrin
authors: N
authors: Motamed
authors: Saeideh
authors: S
authors: Jafarinejad-Farsangi
authors: Ahmadreza
authors: A
authors: Jamshidi
authors: Mahdi
authors: M
authors: Mahmoudi
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000235:genetics*; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000235:genetics; D005260:Female; D005355:Fibrosis / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D058628:Myofibroblasts / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012595:Scleroderma, Systemic / Q000235:genetics*; D012867:Skin / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D014945:Wound Healing / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D051028:bcl-2-Associated X Protein; D016315:Proto-Oncogene Proteins c-abl