title: Advanced glycation end products promote proliferation and suppress autophagy via reduction of Cathepsin D in rat vascular smooth muscle cells.
abstract: Autophagy is closely involved in vascular smooth muscle cell (VSMC) function, but little is known about the association between advanced glycation end products (AGEs) and autophagy and its role in AGEs-induced proliferation and migration of VSMCs. The current study investigated the effects of AGEs on the phenotypic modulation and autophagy of VSMCs, as well as the potential underlying mechanisms. Primary rat VSMCs were treated with bovine serum albumin or AGEs. Cell proliferation was detected by MTT assay, real-time cell analyzer and EdU incorporation. Cell cycle was analyzed by Hoechst staining and flow cytometry. The migration of VSMCs was detected by wound-healing assay and transwell migration assay. LC3 transition and p62 accumulation were detected using Western blotting. Acidic vacuoles were measured using AO and MDC staining. Cathepsin D (CatD) was transduced to VSMCs via lentiviral vectors. AGEs enhanced proliferation and migration of primary rat VSMC in a time-dependent manner. AGEs significantly increased LC3-II transition and p62 expression, as well as accumulation of acidic vacuole, which was not further increased by bafilomycin A1. AGEs decreased CatD expression in a time-dependent pattern, and overexpression of CatD prohibited autophagy attenuation mediated by AGEs. CatD overexpression suppressed AGEs-induced proliferation of VSMCs. Nevertheless, CatD exhibited no effects on AGEs-induced migration of VSMCs. AGEs promote proliferation of VSMCs and suppress autophagy, at least in part via CatD reduction.
authors: Department of Cardiology, The First Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning, People's Republic of China.
authors: Mingfeng
authors: M
authors: Ma
authors: Xiaofan
authors: X
authors: Guo
authors: Ye
authors: Y
authors: Chang
authors: Chao
authors: C
authors: Li
authors: Xin
authors: X
authors: Meng
authors: Si
authors: S
authors: Li
authors: Zhen-Xian
authors: ZX
authors: Du
authors: Hua-Qin
authors: HQ
authors: Wang
authors: Yingxian
authors: Y
authors: Sun
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001343:Autophagy / Q000187:drug effects*; D002402:Cathepsin D / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D018942:Macrolides / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D010588:Phagosomes / Q000187:drug effects / Q000378:metabolism; D051381:Rats
chemical_list: D017127:Glycation End Products, Advanced; D018942:Macrolides; C040929:bafilomycin A1; D002402:Cathepsin D