title: XBP1 splicing triggers miR-150 transfer from smooth muscle cells to endothelial cells via extracellular vesicles.
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 either 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 miR-150-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.
authors.affiliation: Department of Heart Centre, Tianjin Third Central Hospital, Tianjin 300170, China.|Cardiovascular Division, King's College London BHF centre, London SE5 9NU, United Kingdom.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Cardiovascular Division, King's College London BHF centre, London SE5 9NU, United Kingdom.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Cardiovascular Division, King's College London BHF centre, London SE5 9NU, United Kingdom.
authors.forename: Peiyi
authors.initials: P
authors.lastname: Luo
authors.affiliation: Key Laboratory of Artificial Cell, Tianjin Third Central Hospital, Tianjin 300170, China.
authors.forename: Yingtang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Cardiovascular Division, King's College London BHF centre, London SE5 9NU, United Kingdom.
authors.forename: Junyao
authors.initials: J
authors.lastname: Yang
authors.affiliation: Cardiovascular Division, King's College London BHF centre, London SE5 9NU, United Kingdom.
authors.forename: Ka-Hou
authors.initials: KH
authors.lastname: Lao
authors.affiliation: Department of Emergency Medicine, the Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an 710004, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: St George's University of London, London, SW17 0RE, United Kingdom.
authors.forename: Gillian
authors.initials: G
authors.lastname: Cockerill
authors.affiliation: Cardiovascular Division, King's College London BHF centre, London SE5 9NU, United Kingdom.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Cardiovascular Division, King's College London BHF centre, London SE5 9NU, United Kingdom.
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Heart Centre, Tianjin Third Central Hospital, Tianjin 300170, China.|Key Laboratory of Artificial Cell, Tianjin Third Central Hospital, Tianjin 300170, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Li
authors.affiliation: Cardiovascular Division, King's College London BHF centre, London SE5 9NU, United Kingdom.
authors.forename: Lingfang
authors.initials: L
authors.lastname: Zeng
mesh_terms: D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D000067128:Extracellular Vesicles / Q000378:metabolism*; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D012326:RNA Splicing / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D000071717:X-Box Binding Protein 1 / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D000071717:X-Box Binding Protein 1; C533097:MIR150, human; C000605543:XBP1 protein, human