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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

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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.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (Nos. 31071007, 30370578), Science and Technique Foundation of Harbin (Nos. 2008AA3AS097, 2006RFXXS029).

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Authors and Affiliations

  1. Department of Biopharmaceutical Sciences, College of Pharmacy, Harbin Medical University (Daqing), Xinyang Road Gaoxin District, Daqing, 163319, Heilongjiang, People’s Republic of China

    Jingjing Rao, Jing Li, Yun Liu, Ping Lu, Xiaojiao Sun, P. K. Sugumaran & Daling Zhu

  2. Biopharmaceutical Key Laboratory of Heilongjiang Province, Harbin, 150081, People’s Republic of China

    Daling Zhu

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  1. Jingjing Rao
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  2. Jing Li
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  3. Yun Liu
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  6. P. K. Sugumaran
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  7. Daling Zhu
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Correspondence to Daling Zhu.

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Jingjing Rao and Jing Li contributed equally to this study.

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Rao, J., Li, J., Liu, Y. et al. 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. Mol Cell Biochem 367, 9–18 (2012). https://doi.org/10.1007/s11010-012-1313-z

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  • DOI: https://doi.org/10.1007/s11010-012-1313-z

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