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

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.