LncRNA TUG1 regulates autophagy-mediated endothelial-mesenchymal transition of liver sinusoidal endothelial cells by sponging miR-142-3p.
Rui Zhang, Xiaoquan Huang, Yingyi Jiang, Na Li, Jian Wang, Shiyao Chen
Abstract
rat model of cirrhosis, we evaluated autophagy and EndMT in LSECs by immunofluorescence co-localization and immunohistochemical staining. The diagnostic efficiency of miR-142-3p and LPS were determined by receiver-operating characteristic curve analysis. We found that LSECs survived starvation by activating autophagy. LPS treatment enhanced autophagy and promoted EndMT of LSECs by upregulating TUG1. Our rat model of cirrhosis confirmed that serum LPS level, autophagy, and EndMT were increased in LSECs. TUG1 was highly expressed in LSECs, and TUG1 knockdown suppressed ATG5-mediated autophagy and EndMT of LSECs. TUG1 regulated ATG5 via shared miR-142-3p response elements. miR-142-3p was expressed at low levels in LSECs and negatively regulated autophagy and EndMT by reducing ATG5 expression. Our results suggest that TUG1 promotes LPS-induced autophagy and EndMT of LSECs by functioning as an endogenous sponge for miR-142-3p and promoting the expression of ATG5. LPS and miR-142-3p are potential diagnostic and therapeutic targets in cirrhosis.