期刊
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
卷 41, 期 4, 页码 467-475出版社
AMER THORACIC SOC
DOI: 10.1165/rcmb.2008-0333OC
关键词
hypoxia-inducible factor 1 alpha; CapG; transgelin; hypoxia; migration
资金
- Science and Technology Committee of Shanghai, China [06JC14054, 06JC14055]
Hypoxia stimulates the migration of pulmonary artery smooth muscle cells (PASMCs), which contributes to the pathogenesis of pulmonary vessel structural remodeling in hypoxic pulmonary hypertension (HPH). In the present study, we found, using a proteomics-based method, that gelsolin-like actin-capping protein (CapG) and transgelin were preferentially expressed in human (h)PAMSCs under hypoxia compared with normoxia. These two actin-associated proteins, modulate a variety of physiologic processes, including motility of cells, by interacting differently with the actin cytoskeleton. Our study showed that these two genes were up-regulated at both mRNA and protein levels under hypoxia in hPASMCs. As a key transcriptional regulation factor under hypoxia, hypoxia-inducible factor 1 alpha (HIF-1 alpha) up-regulated CapG protein expression under normoxia, and knockdown of HIF-1 alpha expression in hPASMCs also inhibited hypoxia induced CapG up-regulation. However, HIF-1 alpha could not regulate transgelin expression. Reduction of CapG or transgelin expression in hPASMCs by RNA interference was accompanied by significantly impaired migration ability in vitro, especially under hypoxia. Our study demonstrates that CapG and transgelin were preferentially expressed in hPAMSCs under hypoxia compared with normoxia. Hypoxia stimulates expression of these two actin-associated proteins via HIF-1 alpha-dependent and -independent pathways, respectively. The up-regulation of these two proteins may contribute to the increased motility of hPASMCs under hypoxia. These findings may contribute to the understanding of the pathogenesis of HPH.
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