title: Effect of PGC-1α on proliferation, migration, and transdifferentiation of rat vascular smooth muscle cells induced by high glucose.
abstract: We assessed the role of PGC-1α (PPARγ coactivator-1 alpha) in glucose-induced proliferation, migration, and inflammatory gene expression of vascular smooth muscle cells (VSMCs). We carried out phagocytosis studies to assess the role of PGC-1α in transdifferentiation of VSMCs by flow cytometry. We found that high glucose stimulated proliferation, migration and inflammatory gene expression of VSMCs, but overexpression of PGC-1α attenuated the effects of glucose. In addition, overexpression of PGC-1α decreased mRNA and protein level of VSMCs-related genes, and induced macrophage-related gene expression, as well as phagocytosis of VSMCs. Therefore, PGC-1α inhibited glucose-induced proliferation, migration and inflammatory gene expression of VSMCs, which are key features in the pathology of atherosclerosis. More importantly, PGC-1α transdifferentiated VSMCs to a macrophage-like state. Such transdifferentiation possibly increased the portion of VSMCs-derived foam cells in the plaque and favored plaque stability.
authors.affiliation: Jiangsu Diabetes Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Qi
authors.forename: Yujing
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Dongxia
authors.initials: D
authors.lastname: Hou
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D002468:Cell Physiological Phenomena / Q000187:drug effects / Q000235:genetics; D054338:Cell Transdifferentiation; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010587:Phagocytosis / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D018932:Chemokine CCL2; D015850:Interleukin-6; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D005947:Glucose