Article abstract
Nature Cell Biology 6, 872 - 883 (2004)
Published online: 22 August 2004 | doi:10.1038/ncb1161
Dysregulation of HSG triggers vascular proliferative disorders
Kuang-Hueih Chen1,2, Xiaomei Guo2, Dalong Ma3, Yanhong Guo1, Qian Li1, Dongmei Yang2, Pengfei Li1, Xiaoyan Qiu3, Shaojun Wen1, Rui-Ping Xiao1,2 & Jian Tang1
Abstract
Vascular proliferative disorders, such as atherosclerosis and restenosis, are the most common causes of severe cardiovascular diseases, but a common molecular mechanism remains elusive. Here, we identify and characterize a novel hyperplasia suppressor gene, named HSG (later re-named rat mitofusin-2). HSG expression was markedly reduced in hyper-proliferative vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rat arteries, balloon-injured Wistar Kyoto rat arteries, or ApoE-knockout mouse atherosclerotic arteries. Overexpression of HSG overtly suppressed serum-evoked VSMC proliferation in culture, and blocked balloon injury induced neointimal VSMC proliferation and restenosis in rat carotid arteries. The HSG anti-proliferative effect was mediated by inhibition of ERK/MAPK signalling and subsequent cell-cycle arrest. Deletion of the p21ras signature motif, but not the mitochondrial targeting domain, abolished HSG-induced growth arrest, indicating that rHSG-induced anti-proliferation was independent of mitochondrial fusion. Thus, rHSG functions as a cell proliferation suppressor, whereas dysregulation of rHSG results in proliferative disorders.
- The Institute of Cardiovascular Science & The Institute of Molecular Medicine, Peking University, Beijing 100083, China.
- Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
- Center for Human Disease Genomics and Department of Immunology, Health Center of Peking University, Beijing 100083, China.
Correspondence to: Rui-Ping Xiao1,2 e-mail: xiaor@grc.nia.nih.gov
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