title: TGFβ1 induces stress fiber formation through upregulation of TRPC6 in vascular smooth muscle cells.
abstract: Aberrant transforming growth factor β1 (TGFβ1) signaling plays a crucial role in the pathogenesis of vascular fibrosis. On the other hand, deregulated transient receptor potential canonical 6 (TRPC6) channel expression shows impaired vascular physiology and wound healing. However, it has little been known about the functional association between TGFβ1 and TRPC6 in vascular smooth muscle cells (VSMCs). In this study, we analyzed the microarray data obtained from TGFβ1-treated A7r5 VSMCs. We found that TGFβ1 specifically elevates the expression level of TRPC6 mainly through Smad-dependent canonical pathway. The siRNA against TRPC6 abolished TGFβ1-induced molecular and cellular phenotype changes, including myosin light chain phosphorylation, actin stress fiber formation, and cell migration. These results demonstrate that TRPC6 is an important component of TGFβ1 signaling pathway in VSMCs. Therefore, our findings provide a basis for future investigation aimed at developing novel therapeutic strategies for treatment of vascular fibrosis.
authors.affiliation: Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, South Korea.
authors.forename: Soonbum
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, 84112-5650, USA.
authors.forename: Sanghoon
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, South Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Park
authors.affiliation: Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, South Korea.
authors.forename: MinJi
authors.initials: M
authors.lastname: Kang
authors.affiliation: Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, South Korea; Institute of Human-Environment Interface Biology, Seoul National University, Seoul, 03080, South Korea.
authors.forename: Insuk
authors.initials: I
authors.lastname: So
authors.affiliation: Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, South Korea; Institute of Human-Environment Interface Biology, Seoul National University, Seoul, 03080, South Korea. Electronic address: jhjeon2@snu.ac.kr.
authors.forename: Ju-Hong
authors.initials: JH
authors.lastname: Jeon
authors.affiliation: Department of Physiology and Biomedical Sciences, Seoul National University College of Medicine, Seoul, 03080, South Korea; Institute of Human-Environment Interface Biology, Seoul National University, Seoul, 03080, South Korea. Electronic address: jungnyu@snu.ac.kr.
authors.forename: Jung Nyeo
authors.initials: JN
authors.lastname: Chun
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D005355:Fibrosis; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D018994:Myosin Light Chains / Q000378:metabolism; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D022502:Stress Fibers / Q000378:metabolism* / Q000473:pathology; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000199:Actins; D018994:Myosin Light Chains; D034741:RNA, Small Interfering; D051785:Smad Proteins; D050052:TRPC Cation Channels; D053773:Transforming Growth Factor beta1; C492145:Trpc6 protein, rat
keywords: Fibrosis; Stress fiber; TGFβ1; TRPC6; Vascular smooth muscle