Let-7i attenuates human brain microvascular endothelial cell damage in oxygen glucose deprivation model by decreasing toll-like receptor 4 expression

Biochem Biophys Res Commun. 2017 Nov 4;493(1):788-793. doi: 10.1016/j.bbrc.2017.08.093. Epub 2017 Aug 24.

Abstract

The let-7 family of microRNAs (miRNAs) plays an important role on endothelial cell function. However, there have been few studies on their role under ischemic conditions. In this study, we demonstrate that let-7i, belonging to the let-7 family, rescues human brain microvascular endothelial cells (HBMECs) in an oxygen-glucose deprivation (OGD) model. Our data show that the expression of let-7 family miRNAs was downregulated after OGD. Overexpression of let-7i significantly alleviated cell death and improved survival of OGD-treated HBMECs. Let-7i also protected permeability in an in vitro blood brain barrier (BBB) model. Further, let-7i downregulated the expression of toll-like receptor 4 (TLR4), an inflammation trigger. Moreover, overexpression of let-7i decreased matrix metallopeptidase 9 (MMP9) and inducible nitric oxide synthase (iNOS) expression under OGD. Upon silencing TLR4 expression in HBMECs, the anti-inflammatory effect of let-7i was abolished. Our research suggests that let-7i promotes OGD-induced inflammation via downregulating TLR4 expression.

Keywords: Human brain microvascular endothelial cell (HBMEC); Let-7i; Oxygen glucose deprivation (OGD); Toll-like receptor 4 (TLR4).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood-Brain Barrier / metabolism*
  • Blood-Brain Barrier / pathology
  • Brain / blood supply
  • Brain / metabolism*
  • Brain / pathology
  • Brain Ischemia / metabolism*
  • Brain Ischemia / pathology
  • Cells, Cultured
  • Endothelial Cells / metabolism*
  • Endothelial Cells / pathology
  • Glucose / metabolism
  • Humans
  • MicroRNAs / metabolism*
  • Microvessels / metabolism*
  • Microvessels / pathology
  • Oxygen / metabolism
  • Toll-Like Receptor 4 / metabolism*

Substances

  • MicroRNAs
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • mirnlet7 microRNA, human
  • Glucose
  • Oxygen