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XBP1 splicing triggers miR-150 transfer from smooth muscle cells to endothelial cells via extracellular vesicles

Research output: Contribution to journalArticle

Yue Zhao, Yi Li, Peiyi Luo, Yingtang Gao, Junyao Yang, Ka-Hou Lao, Gang Wang, Gillian Cockerill, Yanhua Hu, Qingbo Xu, Tong Li, Lingfang Zeng

Original languageEnglish
Article number28627
JournalScientific Reports
Volume6
Early online date24 Jun 2016
DOIs
Publication statusE-pub ahead of print - 24 Jun 2016

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Abstract

The interaction between endothelial cells (ECs) and smooth muscle cells (SMCs) plays a critical role in the maintenance of vessel wall homeostasis. The X-box binding protein 1 (XBP1) plays an important role in EC and SMC cellular functions. However, whether XBP1 is involved in EC-SMC interaction remains unclear. In this study, In vivo experiments with hindlimb ischemia models revealed that XBP1 deficiency in SMCs significantly attenuated angiogenesis in ischemic tissues, therefore retarded the foot blood perfusion recovery. In vitro studies indicated that ether overexpression of the spliced XBP1 or treatment with platelet derived growth factor-BB up-regulated miR-150 expression and secretion via extracellular vesicles (EVs). The XBP1 splicing-mediated up-regulation of miR-150 might be due to increased stability. The SMC-derived EVs could trigger EC migration, which was abolished by miR-150 knockdown in SMCs, suggesting miR-150 is responsible for SMC-stimulated EC migration. The SMC-derived miR150 containing EVs or premiR-150 transfection increased vascular endothelial growth factor (VEGF)-A mRNA and secretion in ECs. Both inhibitors SU5416 and LY294002 attenuated EVs-induced EC migration. This study demonstrates that XBP1 splicing in SMCs can control EC migration via SMC derived EVs-mediated miR-150 transfer and miR-150-driven VEGF-A/VEGFR/PI3K/Akt pathway activation, thereby modulating the maintenance of vessel wall homeostasis.

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