The phosphorylation of moesin impairs the integrity of vascular basement membrane in pathological angiogenesis

Abstract

Our previous studies demonstrated that advanced glycation end products (AGEs) promote angiogenesis in human umbilical vein endothelial cells (HUVECs) and mouse retina through moesin phosphorylation. AGEs-induced angiogenesis is characterized by abnormal VE-cadherin distribution at adherens junctions and decreased pericytes coverage. In this study, we further investigated the alterations in collagen IV (Col-IV) distribution within the basement membrane (BM) of neovesssles using a HUVECs-retinal microvascular pericytes (RMPs) co-culture system and an AGEs-treated mouse model. The role of moesin phosphorylation in AGEs-induced BM abnormalities was explored through phosphorylation modulation. The results confirmed that AGEs-induced immature angiogenesis in HUVECs-RMPs co-culture system, characterized by decreased pericyte coverage and uneven Col-IV distribution in the neovessel BM. Similar results were observed in retinal vessels from AGEs-treated mice. Modulation of moesin phosphorylation altered the AGEs-induced maldistribution of Col-IV in the vascular BM. We observed obvious co-localization of phosphorylated moesin with heterogenous adhesion molecule CD44 in mouse retinal vessels. This study demonstrates that AGEs induce abnormal distribution of Col-IV in the vascular BM and subsequent neovessel immaturity via phosphorylation of moesin and disruption of heterogenous adhesion junction formation.