Protective effect of microRNA-134-3p on multiple sclerosis through inhibiting PRSS57 and promotion of CD34+ cell proliferation in rats

J Cell Biochem. 2020 Nov;121(11):4347-4363. doi: 10.1002/jcb.29643. Epub 2020 Jul 3.

Abstract

MicroRNAs (miRs) have been extensively studied for their involvement in multiple sclerosis (MS). We investigated the involvement of miR-134-3p on MS. The MS rat model was established, and positive expression of interleukin-17 (IL-17) was detected using the immunohistochemical method while the expression of miR-134-3p and serine protease 57 (PRSS57) was determined by means of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Second, the miR-134-3p overexpression or short hairpin RNA against PRSS57 was introduced into the CD34+ cells to investigate the levels of proliferation and apoptosis-related genes by RT-qPCR and Western blot analysis. In addition, analysis of the targeting relations of miR-134-3p and PRSS57 was conducted using online software and dual-luciferase reporter gene assay. Furthermore, neuronal functions, inflammatory response, proliferation, and apoptosis of CD34+ cells were assayed by flow cytometry, enzyme-linked immunosorbent assay, and methyl thiazolyl tetrazolium. IL-17 and PRSS57 expression increased while miR-134-3p expression decreased in the spinal cord from MS rats. miR-134-3p could target PRSS57. miR-134-3p overexpression or PRSS57 silencing enhanced mitochondrial activity of neurons, mitochondrial membrane potential content, CD34+ cell proliferation, while decreasing Cyt C content, inflammatory response, and cell apoptosis. Collectively, overexpression of miR-134-3p promotes CD34+ cell proliferation via inhibition of PRSS57 in MS, which may serve as a promising target for MS intervention.

Keywords: CD34+ cells; PRSS57; apoptosis; microRNA-134-3p; multiple sclerosis; proliferation.

MeSH terms

  • Animals
  • Antigens, CD34 / metabolism*
  • Apoptosis
  • Cell Proliferation*
  • Disease Models, Animal
  • Gene Expression Regulation, Neoplastic*
  • Male
  • MicroRNAs / genetics*
  • Multiple Sclerosis / therapy*
  • Protective Agents / administration & dosage*
  • Rats
  • Rats, Wistar
  • Serine Proteases / chemistry*

Substances

  • Antigens, CD34
  • MIRN134 microRNA, rat
  • MicroRNAs
  • Protective Agents
  • Serine Proteases