MicroRNA-466 and microRNA-200 increase endothelial permeability in hyperglycemia by targeting Claudin-5
Marisa Kujawa, Megan M. O’Meara, Hainan Li, Liping Xu, Sai Pranathi Meda Venkata, Huong Thanh Nguyen, Morgan Minjares, Kezhong Zhang, Jie‐Mei Wang
Abstract
experiments unveiled higher expressions of miR-200 family members and miR-466 in diabetic ECs and in healthy ECs when exposed to high glucose. Overexpression of both miR-200 and miR-466 significantly increased EC permeability through transcriptional suppression of Claudin-5, the cell tight junction protein, by directly binding to its 3' untranslated region. In a mouse model of chronic hyperglycemia mimicking type 2 diabetes in humans (db/db mice), the delayed closure rate of a full-thickness excisional wound was partly rescued by topical application of the miR-200 inhibitor. The topical application of both miR-200 and miR-466 inhibitors exhibited improved efficacy in accelerating wound closure compared with the topical application of miR-200 inhibitor alone. Our study demonstrated the potentially effective approach of miR-200/miR-466 cocktail inhibition to restore vascular integrity and tissue repair in hyperglycemia.