title: The key role of PGC-1α in mitochondrial biogenesis and the proliferation of pulmonary artery vascular smooth muscle cells at an early stage of hypoxic exposure.
abstract: Peroxisome proliferator activated receptor gamma coactivator 1α (PGC-1α) induced by hypoxia regulates mitochondrial biogenesis and oxidative stress. However, the potential role of PGC-1α in hypoxia-promoted proliferation of pulmonary arterial vascular smooth muscle cells (PASMCs) is completely unknown. In this study, we found that hypoxia significantly induced the expression of PGC-1α in cultured PASMCs and activated mitochondrial biogenesis through upregulation of nuclear respiratory factor-1 and mitochondria transcription factor A in a time-dependent manner. Knockdown of PGC-1α by siRNA abrogated hypoxia-induced PASMCs proliferation via the downregulation of PCNA, cyclinA, and cyclinE. Furthermore, we observed that PI3K/Akt signaling pathway was involved in hypoxia induced PGC-1α expression and PASMCs proliferation. Taken together, these datas reveal PGC-1α as the key regulator to mediate mitochondrial biogenesis and the proliferation of PASMCs at an early stage of hypoxic exposure. This process might bring to light a potential adaptive mechanism for PASMCs to minimize hypoxic damage and our novel findings provide new insight into the development of hypoxic pulmonary hypertension.
authors.affiliation: Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Gaoxin District, Daqing, Heilongjiang, People's Republic of China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Rao
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.forename: Ping
authors.initials: P
authors.lastname: Lu
authors.forename: Xiaojiao
authors.initials: X
authors.lastname: Sun
authors.forename: P K
authors.initials: PK
authors.lastname: Sugumaran
authors.forename: Daling
authors.initials: D
authors.lastname: Zhu
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D049109:Cell Proliferation; D002478:Cells, Cultured; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology*; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation
chemical_list: D016213:Cyclins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt