Schisandrin B suppresses TGFβ1-induced stress fiber formation by inhibiting myosin light chain phosphorylation

Jung Nyeo Chun, Sang Yeob Kim, Eun Jung Park, Eun Jung Kwon, Dong Jun Bae, In San Kim, Hye Kyung Kim, Jong Kwan Park, Sung Won Lee, Hyun Ho Park, Insuk So, Ju Hong Jeon

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 β1 (TGFβ1)-mediated cellular changes are closely associated with the pathogenesis of vascular fibrotic diseases. Particularly, TGFβ1 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 TGFβ1-induced stress fiber assembly in A7r5 VSMCs. Materials and methods To investigate pharmacological actions of SCE and its ingredients on TGFβ1-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 TGFβ1-induced stress fiber formation and cell migration. Schisandrin B (SchB) showed the most prominent effect among the active ingredients of SCE tested. SchB reduced TGFβ1-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 TGFβ1-mediated induction of α-smooth muscle actin by inhibiting Smad signaling. Conclusions The present study demonstrates that SCE and its active ingredient SchB suppressed TGFβ1-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.

Original languageEnglish
Pages (from-to)364-371
Number of pages8
JournalJournal of Ethnopharmacology
Volume152
Issue number2
DOIs
Publication statusPublished - 2014 Mar 14
Externally publishedYes

Keywords

  • Schisandra chinensis
  • Schisandrin B
  • Stress fiber
  • TGFβ1
  • Vascular fibrosis
  • Vascular smooth muscle cell

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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  • Cite this

    Chun, J. N., Kim, S. Y., Park, E. J., Kwon, E. J., Bae, D. J., Kim, I. S., Kim, H. K., Park, J. K., Lee, S. W., Park, H. H., So, I., & Jeon, J. H. (2014). Schisandrin B suppresses TGFβ1-induced stress fiber formation by inhibiting myosin light chain phosphorylation. Journal of Ethnopharmacology, 152(2), 364-371. https://doi.org/10.1016/j.jep.2014.01.024