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Significance The crosstalk between vascular endothelial cells (ECs) and pericytes in the microvascular is critical for vascular homeostasis and remodeling. However, the crosstalk between these two cells is often disrupted by diabetes, resulting in severe and even lethal vascular defects. Here, we show that diabetes-related stress up-regulates cPWWP2A expression in pericytes but not in ECs. Pericyte-derived cPWWP2A affects pericyte coverage and vascular integrity through interacting with miR-579 and its target genes, including angiopoietin 1/occludin/SIRT1. Our study thus reveals a critical role of cPWWP2A-mediated signaling in retinal microvascular dysfunction and implies potential therapeutic benefit with high-level expression of cPWWP2A or reduced miR-579 expression.

Targeting pericyte–endothelial cell crosstalk by circular RNA-cPWWP2A inhibition aggravates diabetes-induced microvascular dysfunction