MiR-128-1-5p regulates tight junction induced by selenium deficiency via targeting cell adhesion molecule 1 in broilers vein endothelial cells.

Abstract

Vein endothelial cells (VECs)constitute an important barrier for macromolecules and circulating cells from the blood to the tissues, stabilizing the colloid osmotic pressure of the blood, regulating the vascular tone, and rapidly changing the intercellular connection, and maintaining normal physiological function. Tight junction has been discovered as an important structural basis of intercellular connection and may play a key role in intercellular connection injuries or vascular diseases and selenium (Se) deficiency symptoms. Hence, we replicated the Se-deficient broilers modeland detected the specific microRNA in response to Se-deficient vein by using quantitative real time-PCR (qRT-PCR) analysis. Also, we selected miR-128-1-5p based on differential expression in vein tissue and confirmed its target gene cell adhesion molecule 1 (CADM1) by the dual luciferase reporter assay and qRT-PCR in VECs. We made the ectopic miR-128-1-5p expression for the purpose of validating its function on tight junction. The result showed that miR-128-1-5p and CADM1 were involved in the ZO-1-mediated tight junction, increased paracellular permeability, and arrested cell cycle. We presumed that miR-128-1-5p and Se deficiency might trigger tight junction. Interestingly, miR-128-1-5p inhibitor and fasudil in part hinder the destruction of theintercellular structure caused by Se deficiency. The miR-128-1-5p/CADM1/tight junction axis provides a new avenue toward understanding the mechanism of Se deficiency, revealing a novel regulation model of tight junction injury in vascular diseases.