c-Ski inhibits autophagy of vascular smooth muscle cells induced by oxLDL and PDGF

• Published in: PloS one 2014-06, Vol.9 (6), p.e98902-e98902
• Main Authors: Li, Jun, Zhao, Li, Yang, Ting, Zeng, Yi-Jun, Yang, Kang
• Format: Article
• Language: English
• Subjects: AKT protein; Animals; Aorta; Aorta - cytology; Apoptosis; Atherosclerosis; Autophagy; Biochemistry; Biocompatibility; Biology and Life Sciences; Biomedical materials; Cell death; Cell Proliferation; Cells, Cultured; Coronary vessels; Down-Regulation; Experiments; Growth factors; Heart surgery; Kinases; Lipoproteins; Lipoproteins, LDL - pharmacology; Low density lipoproteins; Medicine and Health Sciences; Molecular biology; Muscle contraction; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - metabolism; Muscles; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - metabolism; Osteopontin; Phagocytosis; Phosphorylation; Platelet-derived growth factor; Platelet-Derived Growth Factor - pharmacology; Proliferating cell nuclear antigen; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - physiology; Rats; RNA-mediated interference; Smooth muscle; Studies; Transforming growth factor-b; Up-Regulation
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0098902

Autophagy is increasingly being recognized as a critical determinant of vascular smooth muscle cell (VSMC) biology. Previously, we have demonstrated that c-Ski inhibits VSMC proliferation stimulated by transforming growth factor β (TGF-β), but it is not clear whether c-Ski has the similar protective role against other vascular injury factors and whether regulation of autophagy is involved in its protective effects on VSMC. Accordingly, in this study, rat aortic A10 VSMCs were treated with 40 µg/ml oxidized low-density lipoprotein (oxLDL) or 20 ng/ml platelet-derived growth factor (PDGF), both of which were autophagy inducers and closely related to the abnormal proliferation of VSMCs. Overexpression of c-Ski in A10 cells significantly suppressed the oxLDL- and PDGF- induced autophagy. This action of c-Ski resulted in inhibiting the cell proliferation, the decrease of contractile phenotype marker α-SMA expression while the increase of synthetic phenotype marker osteopontin expression stimulated by oxLDL or PDGF. Inversely, knockdown of c-Ski by RNAi enhanced the stimulatory effects of oxLDL or PDGF on A10 cell growth and phenotype transition. And further investigation found that inhibition of AKT phosphorylation to downregulate proliferating cell nuclear antigen (PCNA) expression, was involved in the regulation of autophagy and associated functions by c-Ski in the oxLDL- and PDGF-stimulated VSMCs. Collectively, c-Ski may play an important role in inhibiting autophagy to protect VSMCs against some harsh stress including oxLDL and PDGF.