miR-135b-dependent downregulation of S100B promotes neural stem cell differentiation in a hypoxia/ischemia-induced cerebral palsy rat model

Am J Physiol Cell Physiol. 2020 Dec 1;319(6):C955-C966. doi: 10.1152/ajpcell.00481.2019. Epub 2020 Jun 3.


Cerebral palsy (CP) is frequently caused by brain injury during pregnancy, delivery, or the immediate postnatal period. The differentiation potential of neural stem cell (NSC) makes them effective in restoring injured tissues and organs with minimal risks of side effects. In this study, we identified a novel microRNA-135b (miR-135b) in CP and investigated its functional role in mediating NSC differentiation. CP models were established in Wistar rats and validated with the Y-maze test. Gain- and loss-of-function experimentation was performed on CP rats. Then NSCs were isolated and the expression patterns of miR-135b and S100B were altered in NSCs. S100B exhibited high expression in the hippocampus tissues of CP models, which was targeted by miR-135b. miR-135b elevation or S100B silencing resulted in promoted NSC differentiation, alleviated brain injury, and inhibited NSC apoptosis in hippocampus tissues of CP rats. S100B downregulation targeted by miR-135b overexpression contributed to the inactivation of the signal transducer and activator of transcription-3 (STAT3) pathway, which promoted NSC differentiation and proliferation but inhibited NSC apoptosis. Our results highlight the suppressor role played by miR-135b in CP by inducing NSC differentiation via inactivation of S100B-dependent STAT3 pathway.

Keywords: S100B; cerebral palsy; microRNA-135b; signal transducer and activator of transcription-3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Cell Differentiation / genetics*
  • Cell Proliferation / genetics
  • Cerebral Palsy / genetics*
  • Cerebral Palsy / pathology
  • Disease Models, Animal
  • Down-Regulation / genetics*
  • Gene Expression Regulation, Neoplastic / genetics
  • Hypoxia / genetics*
  • Hypoxia / pathology
  • Ischemia / genetics
  • Ischemia / pathology
  • Male
  • MicroRNAs / genetics*
  • Neural Stem Cells / pathology*
  • Rats
  • Rats, Wistar
  • S100 Calcium Binding Protein beta Subunit / genetics*
  • STAT3 Transcription Factor
  • Signal Transduction / genetics


  • MIRN135 microRNA, rat
  • MicroRNAs
  • S100 Calcium Binding Protein beta Subunit
  • S100b protein, rat
  • STAT3 Transcription Factor