NF-κB-upregulated miR-155-5p promotes hepatocyte mitochondrial dysfunction to accelerate the development of nonalcoholic fatty liver disease through downregulation of STC1

Previous studies have highlighted the involvement of nuclear factor kappa B (NF-kappa B) in the development of nonalcoholic fatty liver disease (NAFLD). The purpose of our investigation is to explore the interaction among NF-kappa B, microRNA-155-5p (miR-155-5p), and Stanniocalcin 1 (STC1), and its effects on NAFLD by establishing a NAFLD model in Sprague Dawley rats. A highly-expressed miR-155-5p and NF-kappa B was revealed in the liver tissues of NAFLD rats, and a positive correlation was identified between miR-155-5p and NF-kappa B. Next, the expression of NF-kappa B and STC1 was altered in the modeled rats through lentivirus injection, followed by determination on the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol, triglycerides, and low-density lipoprotein cholesterol. Furthermore, the hepatocyte mitochondria were separated to measure the activities of adenosine triphosphate (ATP), reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and mitochondrial respiratory chain complex, and to observe the number, length and ultrastructural length of mitochondrial cristae. The results demonstrated that NF-kappa B overexpression induced mitochondrial dysfunction, increased ROS level, decreased ATP and MMP contents, as well as inhibited the number and length of mitochondrial cristae in the hepatocyte mitochondria of NAFLD rats. Besides, miR-155-5p was found to negatively regulate STC1 expression based on dual luciferase reporter gene assay, which exert inhibition on mitochondrial activity of hepatocytes in NAFLD rats. These results uncover the possible involvement of NF-kappa B/miR-155-5p/STC1 axis in NAFLD progression, that NF-kappa B could increase miR-155-5p expression to inhibit STC1 expression, thus inducing hepatic mitochondrial dysfunction and promoting the occurrence and development of NAFLD.

Automated summary

This study reveals the potential involvement of the NF-kappa B/miR-155-5p/STC1 axis in the progression of NAFLD. It suggests that increased expression of miR-155-5p induced by NF-kappa B inhibits STC1 expression, resulting in hepatic mitochondrial dysfunction and promoting the occurrence and development of NAFLD.