P75(NTR)-dependent activation of NF-κB regulates microRNA-503 transcription and pericyte-endothelial crosstalk in diabetes after limb ischaemia.

ABSTRACT: The communication between vascular endothelial cells (ECs) and pericytes in the microvasculature is fundamental for vascular growth and homeostasis; however, these processes are disrupted by diabetes. Here we show that modulation of p75(NTR) expression in ECs exposed to high glucose activates transcription of miR-503, which negatively affects pericyte function. p75(NTR) activates NF-κB to bind the miR-503 promoter and upregulate miR-503 expression in ECs. NF-κB further induces activation of Rho kinase and shedding of endothelial microparticles carrying miR-503, which transfer miR-503 from ECs to vascular pericytes. The integrin-mediated uptake of miR-503 in the recipient pericytes reduces expression of EFNB2 and VEGFA, resulting in impaired migration and proliferation. We confirm operation

SUBMITTER: Caporali A 

PROVIDER: S-EPMC4538859 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature