Matrix Stiffness Regulates Endothelial Cell Proliferation through Septin 9

Yi Ting Yeh, Sung Sik Hur, Joann Chang, Kuei Chun Wang, Jeng Jiann Chiu, Yi Shuan Li, Shu Chien

研究成果: 雜誌貢獻文章

65 引文 斯高帕斯(Scopus)

摘要

Endothelial proliferation, which is an important process in vascular homeostasis, can be regulated by the extracellular microenvironment. In this study we demonstrated that proliferation of endothelial cells (ECs) was enhanced on hydrogels with high stiffness (HSG, 21.5 kPa) in comparison to those with low stiffness (LSG, 1.72 kPa). ECs on HSG showed markedly prominent stress fibers and a higher RhoA activity than ECs on LSG. Blockade of RhoA attenuated stress fiber formation and proliferation of ECs on HSG, but had little effect on ECs on LSG; enhancement of RhoA had opposite effects. The phosphorylations of Src and Vav2, which are positive RhoA upstream effectors, were higher in ECs on HSG. The inhibition of Src/Vav2 attenuated the HSG-mediated RhoA activation and EC proliferation but exhibited nominal effects on ECs on LSG. Septin 9 (SEPT9), the negative upstream effector for RhoA, was significantly higher in ECs on LSG. The inhibition of SEPT9 increased RhoA activation, Src/Vav2 phosphorylations, and EC proliferation on LSG, but showed minor effects on ECs on HSG. We further demonstrated that the inactivation of integrin αvβ3 caused an increase of SEPT9 expression in ECs on HSG to attenuate Src/Vav2 phosphorylations and inhibit RhoA-dependent EC proliferation. These results demonstrate that the SEPT9/Src/Vav2/RhoA pathway constitutes an important molecular mechanism for the mechanical regulation of EC proliferation.

原文英語
文章編號e46889
期刊PLoS ONE
7
發行號10
DOIs
出版狀態已發佈 - 十月 31 2012
對外發佈Yes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Yeh, Y. T., Hur, S. S., Chang, J., Wang, K. C., Chiu, J. J., Li, Y. S., & Chien, S. (2012). Matrix Stiffness Regulates Endothelial Cell Proliferation through Septin 9. PLoS ONE, 7(10), [e46889]. https://doi.org/10.1371/journal.pone.0046889