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

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-1 alpha 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 cMet 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.

Automated summary

This study investigates the effect of chemically-induced hypoxia on the expression of miRNA molecules in human endothelial cells and identifies several miRNAs that may affect the HGFA-HGF-c-Met signaling pathway. The findings shed new light on the role of miRNAs in hypoxia and highlight the importance of specific miRNAs in regulating this signaling pathway.