Role of hypoxia on microRNA-dependant regulation of HGFA - HGF - c-Met signalling pathway in human progenitor and mature endothelial cells

Int J Biochem Cell Biol. 2022 Nov:152:106310. doi: 10.1016/j.biocel.2022.106310. Epub 2022 Sep 28.

Abstract

Hepatocyte growth factor (HGF) is considered to be one of the key pro-angiogenic cytokines that stimulates endothelial cells to proliferate and migrate. The activation of the precursor form of HGF is primarily undertaken by the serine protease HGFA. Research indicates that HIF-1α hypoxia stimulates the expression of HGFA, which is synthesized by a range of cells including fibroblasts, endothelium, and macrophages. To date, little is known about the potential role of epigenetic factors in the regulation of the HGFA - HGF - c-Met signalling pathway. The literature suggests that there are several microRNAs (miRNAs, miRs) directly affecting the expression of c-Met under normoxic conditions. The main objective of the research described was to explore the effect of chemically-induced hypoxia on the expression of miRNA molecules in human progenitor and mature endothelial cells, with particulate attention paid to those miRNAs that may specifically affect the HGFA - HGF - c-Met signalling pathway. This publication sheds new light on the role of miRNAs in hypoxia, as well as identifying several miRNAs directly involved in the regulation of HGFA, HGF and c-Met expression in hypoxic conditions. The results indicate that hsa-miR-335-5p, hsa-miR-425-5p and hsa-miR-101-3p are the major miRNAs that appear to play an important role in the regulation of the HGFA - HGF - c-Met signalling pathway.

Keywords: Angiogenesis; Endothelial cells; Hypoxia; MicroRNA.

MeSH terms

  • Endothelial Cells* / metabolism
  • Endothelial Progenitor Cells / metabolism
  • Hepatocyte Growth Factor* / genetics
  • Hepatocyte Growth Factor* / metabolism
  • Humans
  • Hypoxia* / chemically induced
  • Hypoxia* / genetics
  • Hypoxia* / metabolism
  • Membrane Glycoproteins / genetics
  • MicroRNAs* / genetics
  • Proto-Oncogene Proteins c-met* / genetics
  • Proto-Oncogene Proteins c-met* / metabolism
  • Signal Transduction

Substances

  • Hepatocyte Growth Factor
  • HGF protein, human
  • HIF1A protein, human
  • Membrane Glycoproteins
  • MicroRNAs
  • MIRN101 microRNA, human
  • MIRN335 microRNA, human
  • MIRN425 microRNA, human
  • Proto-Oncogene Proteins c-met