High glucose promotes hepatic fibrosis via miR‑32/MTA3‑mediated epithelial‑to‑mesenchymal transition

Mol Med Rep. 2019 Apr;19(4):3190-3200. doi: 10.3892/mmr.2019.9986. Epub 2019 Feb 25.

Abstract

Hepatic fibrosis is characterized by the aberrant production and deposition of extracellular matrix (ECM) proteins. Growing evidence indicates that the epithelial‑mesenchymal transition serves a crucial role in the progression of liver fibrogenesis. Although a subset of microRNAs (miRNAs or miRs) has recently been identified as essential regulators of the EMT gene expression, studies of the EMT in hyperglycemic‑induced liver fibrosis are limited. In the current study, it was observed that high glucose‑treated AML12 cells occurred EMT process, and miR‑32 expression was markedly increased in the liver tissue of streptozotocin‑induced diabetic rats and in high glucose‑treated AML12 cells. Additionally, the contribution of the EMT to liver fibrosis by targeting metastasis‑associated gene 3 (MTA3) under hyperglycemic conditions was suppressed by AMO‑32. The results indicated that miR‑32 and MTA3 may be considered as novel drug targets in the prevention and treatment of liver fibrosis under hyperglycemic conditions. These finding improves the understanding of the progression of liver fibrogenesis.

MeSH terms

  • Animals
  • Biomarkers
  • Cells, Cultured
  • Diabetes Mellitus, Experimental
  • Disease Models, Animal
  • Disease Progression
  • Disease Susceptibility
  • Epithelial-Mesenchymal Transition / genetics*
  • Gene Expression Regulation
  • Glucose / adverse effects
  • Glucose / metabolism*
  • Hyperglycemia / complications
  • Hyperglycemia / metabolism
  • Liver Cirrhosis / etiology*
  • Liver Cirrhosis / metabolism*
  • Liver Cirrhosis / pathology
  • Male
  • MicroRNAs / genetics*
  • Neoplasm Proteins / genetics*
  • RNA Interference
  • Rats

Substances

  • Biomarkers
  • MIRN32 microRNA, rat
  • MicroRNAs
  • Neoplasm Proteins
  • Glucose