Schisandrin B suppresses TGF beta 1-induced stress fiber formation by inhibiting myosin light chain phosphorylation

Title
Schisandrin B suppresses TGF beta 1-induced stress fiber formation by inhibiting myosin light chain phosphorylation
Author(s)
박현호전주홍[ 전주홍]서인석[서인석]천정녀[천정녀]김상엽[김상엽]박은정[박은정]권은정[권은정]배동준[배동준]김인산[김인산]김혜경[김혜경]박종관[박종관]이성원[이성원]
Keywords
VASCULAR SMOOTH-MUSCLE; TGF-BETA; CHINENSIS EXTRACT; BARRIER FUNCTION; RHO-KINASE; CELLS; EXPRESSION; MIGRATION; DISEASE; PERMEABILITY
Issue Date
201403
Publisher
ELSEVIER IRELAND LTD
Citation
JOURNAL OF ETHNOPHARMACOLOGY, v.152, no.2, pp.364 - 371
Abstract
Ethnopharmacological relevance: Schisandra chinensis fruit extract (SCE) has been used as a traditional oriental medicine for treating vascular diseases. However, the pharmacologic effects and mechanisms of SCE on vascular fibrosis are still largely unknown. Transforming growth factor beta 1 (TGF beta 1)-mediated cellular changes are closely associated with the pathogenesis of vascular fibrotic diseases. Particularly, TGF beta 1 induces actin stress fiber formation that is a crucial mechanism underlying vascular smooth muscle cell (VSMC) migration in response to vascular injury. In this study, we investigated the effect of SCE and its active ingredients on TGF beta 1-induced stress fiber assembly in A7r5 VSMCs. Materials and methods: To investigate pharmacological actions of SCE and its ingredients on TGF beta 1-treated VSMCs, we have employed molecular and cell biological technologies, such as confocal microscopy, fluorescence resonance energy transfer, western blotting, and radiometric enzyme analyses. Results: We found that SCE inhibited TGF beta 1-induced stress fiber formation and cell migration. Schisandrin B (SchB) showed the most prominent effect among the active ingredients of SCE tested. SchB reduced TGF beta 1-mediated phosphorylation of myosin light chain, and this effect was independent of RhoA/Rho-associated kinase pathway. Fluorescence resonance energy transfer and radiometric enzyme assays confirmed that SchB inhibited myosin light chain kinase activity. We also showed that SchB decreased TGF beta 1-mediated induction of alpha-smooth muscle actin by inhibiting Smad signaling. Conclusions: The present study demonstrates that SCE and its active ingredient SchB suppressed TGF beta 1-induced stress fiber formation at the molecular level. Therefore, our findings may help future investigations to develop multi-targeted therapeutic strategies that attenuate VSMC migration and vascular fibrosis. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/32820http://dx.doi.org/10.1016/j.jep.2014.01.024
ISSN
0378-8741
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이과대학 > 화학생화학부 > Articles
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