Resveratrol contributes to the inhibition of liver fibrosis by inducing autophagy via the microRNA‑20a‑mediated activation of the PTEN/PI3K/AKT signaling pathway

Int J Mol Med. 2020 Dec;46(6):2035-2046. doi: 10.3892/ijmm.2020.4748. Epub 2020 Oct 9.

Abstract

Liver fibrosis (LF) is a healing response to wounds resulting in liver injury that can cause liver failure or even cancer without functional prevention. Resveratrol (RSV) has been suggested to exert biological effects against various human diseases. MicroRNA‑20a (miRNA/miR‑20a) has been shown to promote disease progression. The present study aimed to assess the mechanisms through which RSV induces autophagy and activates the miR‑20a‑mediated phosphatase and tensin homolog (PTEN)/PI3K/AKT signaling pathway in LF. First, a rat model of carbon tetrachloride (CCL4)‑induced LF and a cell model of platelet‑derived growth factor (PDGF)‑BB‑stimulated HSC‑T6 cells were established for use in subsequent experiments. Subsequently, RSV at a range of concentrations was injected into the model rats with LF. Indicators related to liver injury, oxidative stress and fibrosis were determined in the rats with LF. The RSV‑treated HSC‑T6 cells were subjected to transfection with miR‑20a mimic and PTEN overexpression plasmid to assess the levels of liver injury and LF. A dual‑luciferase reporter gene assay was performed to verify the binding sites between PTEN and miR‑20a. RSV was found to alleviate LF in rats, and autophagy was enhanced in the rats with LF following RSV treatment. Furthermore, the activation of the PTEN/PI3K/AKT axis attenuated LF, which was reversed by transfection with miR‑20a mimic. RSV reversed the inhibitory effects of miR‑20a on PTEN expression, reducing miR‑20a expression and promoting PTEN, PI3K and p‑AKT protein expression, thus attenuating LF. On the whole, the present study demonstrates that RSV induces autophagy and activates the miR‑20a‑mediated PTEN/PI3K/AKT signaling pathway to attenuate LF. These findings may lead to the development of potential therapeutic strategies for LF.

MeSH terms

  • Animals
  • Autophagy* / drug effects
  • Autophagy* / genetics
  • Base Sequence
  • Cell Line
  • Down-Regulation / drug effects
  • Liver / drug effects
  • Liver / pathology
  • Liver / ultrastructure
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / pathology*
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • PTEN Phosphohydrolase / metabolism*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats, Sprague-Dawley
  • Resveratrol / pharmacology
  • Resveratrol / therapeutic use*
  • Signal Transduction / drug effects

Substances

  • MIRN20 microRNA, rat
  • MicroRNAs
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • Resveratrol