microRNA-130b May Induce Cerebral Vasospasm after Subarachnoid Hemorrhage via Modulating Kruppel-like Factor 4

Mol Cell Biol. 2023;43(7):301-316. doi: 10.1080/10985549.2023.2210030. Epub 2023 Jun 29.

Abstract

Recently, the diverse functions of microRNAs (miRNAs) in brain diseases have been demonstrated. We intended to uncover the functional role of microRNA-130b (miR-130b) in cerebral vasospasm (CVS) following subarachnoid hemorrhage (SAH). SAH was induced by injecting the autologous blood into the cisterna magna of Sprague Dawley rats. The cerebral vascular smooth muscle cells (cVSMCs) were extracted for in vitro experimentation. In vitro and in vivo assays were implemented with transfection of miR-130b mimic/inhibitor, sh-Kruppel-like factor 4 (KLF4), oe-KLF4 plasmids or p38/MAPK signaling pathway agonist (anisomycin), respectively, to elaborate the role of miR-130b in CVS following SAH. Elevated miR-130b and reduced KLF4 were found in SAH patients and rat models of SAH. KLF4 was the target gene of miR-130b. miR-130b promoted the proliferation and migration of cVSMCs through the Inhibition of KLF4. Besides, KLF4 inhibited the proliferation and migration of cVSMCs through blockage of the p38/MAPK pathway. Furthermore, in vivo assay confirmed the inhibitory effect of decreased miR-130b in CVS following SAH. In conclusion, miR-130b may activate the p38/MAPK signaling pathway through targeted inhibition of KLF4, thereby contributing to some extent to the development of cerebral vasospasm after SAH.

Keywords: KLF4; cerebral vasospasm; microRNA-130b; p38/MAPK signaling pathway; subarachnoid hemorrhage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Kruppel-Like Factor 4
  • MicroRNAs* / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Subarachnoid Hemorrhage* / complications
  • Subarachnoid Hemorrhage* / genetics
  • Subarachnoid Hemorrhage* / metabolism
  • Vasospasm, Intracranial* / genetics
  • Vasospasm, Intracranial* / metabolism

Substances

  • Kruppel-Like Factor 4
  • MicroRNAs
  • Klf4 protein, rat

Associated data

  • figshare/10.6084/m9.figshare.227078

Grants and funding

This work is supported by Shenzhen Key Laboratory of Prevention and Treatment of Severe Infections [ZDSYS20200811142804014]; Shenzhen Key Medical Discipline Construction Fund [SZXK045]; General project of Shenzhen Nature Fund [JCYJ20210324114008023]; Special [2022N070] Research, development and application of low-injury interventional embolization system for ischemic stroke..