caa a22 4500 606234403 CHVBK 20210128101237.0 cr unu---uuuuu 210128e20150701xx s 000 0 eng 10.1007/s11010-015-2408-0 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2408-0 c-Abl silencing reduced the inhibitory effects of TGF-β1 on apoptosis in systemic sclerosis dermal fibroblasts [Elektronische Daten] [Elham Karimizadeh, Farhad Gharibdoost, Nasrin Motamed, Saeideh Jafarinejad-Farsangi, Ahmadreza Jamshidi, Mahdi Mahmoudi] 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. Springer Science+Business Media New York, 2015 Systemic sclerosis nationallicence Apoptosis nationallicence TGF-β1 nationallicence c-Abl nationallicence Fibroblast nationallicence Bax/Bcl-2 ratio nationallicence Karimizadeh Elham Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, P.O. Box 141556455, Tehran, Iran aut Gharibdoost Farhad Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Kargar Ave, P.O. Box 1411713137, Tehran, Iran aut Motamed Nasrin Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, P.O. Box 141556455, Tehran, Iran aut Jafarinejad-Farsangi Saeideh Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, P.O. Box 141556455, Tehran, Iran aut Jamshidi Ahmadreza Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Kargar Ave, P.O. Box 1411713137, Tehran, Iran aut Mahmoudi Mahdi Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Kargar Ave, P.O. Box 1411713137, Tehran, Iran aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 405/1-2(2015-07-01), 169-176 0300-8177 405:1-2<169 2015 405 11010 https://doi.org/10.1007/s11010-015-2408-0 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2408-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Karimizadeh Elham Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, P.O. Box 141556455, Tehran, Iran aut NATIONALLICENCE 700 1- Gharibdoost Farhad Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Kargar Ave, P.O. Box 1411713137, Tehran, Iran aut NATIONALLICENCE 700 1- Motamed Nasrin Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, P.O. Box 141556455, Tehran, Iran aut NATIONALLICENCE 700 1- Jafarinejad-Farsangi Saeideh Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, P.O. Box 141556455, Tehran, Iran aut NATIONALLICENCE 700 1- Jamshidi Ahmadreza Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Kargar Ave, P.O. Box 1411713137, Tehran, Iran aut NATIONALLICENCE 700 1- Mahmoudi Mahdi Rheumatology Research Center, Shariati Hospital, Tehran University of Medical Sciences, Kargar Ave, P.O. Box 1411713137, Tehran, Iran aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 405/1-2(2015-07-01), 169-176 0300-8177 405:1-2<169 2015 405 11010