title: Up-regulation of two actin-associated proteins prompts pulmonary artery smooth muscle cell migration under hypoxia.
abstract: 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 1alpha (HIF-1alpha) up-regulated CapG protein expression under normoxia, and knockdown of HIF-1alpha expression in hPASMCs also inhibited hypoxia induced CapG up-regulation. However, HIF-1alpha 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-1alpha-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.
authors.affiliation: Department of Respiratory Medicine, Ruijin Hospital, Medical School of Shanghai Jiaotong University, N0.197, The Second Ruijin Road, Shanghai, 200025, China.
authors.forename: Ruifeng
authors.initials: R
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.forename: Qingyun
authors.initials: Q
authors.lastname: Li
authors.forename: Jialin
authors.initials: J
authors.lastname: Liu
authors.forename: Weiyan
authors.initials: W
authors.lastname: Yao
authors.forename: Huanying
authors.initials: H
authors.lastname: Wan
mesh_terms: D015687:Cell Hypoxia / Q000235:genetics*; D002465:Cell Movement; D002478:Cells, Cultured / Q000378:metabolism; D006801:Humans; D006976:Hypertension, Pulmonary / Q000473:pathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology; D008840:Microfilament Proteins / Q000096:biosynthesis* / Q000235:genetics; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000502:physiology*; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D011651:Pulmonary Artery / Q000166:cytology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000494:pharmacology; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008840:Microfilament Proteins; D009124:Muscle Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C051615:transgelin; C066575:CAPG protein, human