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Pirfenidone modifies hepatic miRNAs expression in a model of MAFLD/NASH

Rebeca Escutia-Gutiérrez1, J Samael Rodríguez-Sanabria1, C Alejandra Monraz-Méndez1

  • 1Department of Molecular Biology and Genomics, Institute for Molecular Biology in Medicine and Gene Therapy, Health Sciences University Center, University of Guadalajara, Guadalajara, Jalisco, Mexico.

Scientific Reports
|June 4, 2021
PubMed

Insights

Prolonged-release pirfenidone (PR-PFD) treatment reduced key hepatic microRNAs (miRNAs) and reversed metabolic pathway modifications in a mouse model of metabolic associated fatty liver disease (MAFLD) and nonalcoholic steatohepatitis (NASH).

Area of Science:

  • Hepatology
  • Molecular Biology
  • Pharmacology

Background:

  • MicroRNAs (miRNAs) play a crucial role in the pathogenesis of metabolic associated fatty liver disease (MAFLD) and nonalcoholic steatohepatitis (NASH).
  • Understanding the impact of therapeutic interventions on miRNA expression is vital for developing effective treatments for these conditions.

Purpose of the Study:

  • To investigate the effects of prolonged-release pirfenidone (PR-PFD) on hepatic miRNA expression in a preclinical model of MAFLD/NASH.
  • To evaluate the impact of PR-PFD on gene expression pathways related to lipid metabolism, inflammation, and fibrosis in MAFLD/NASH.

Main Methods:

  • A high-fat and high-carbohydrate diet (HFD) was used to induce MAFLD/NASH in male C57BL/6J mice for 16 weeks.
  • Mice were treated with PR-PFD (300 mg/kg/day) from week 8 to week 16.
  • Hepatic miRNA and target gene expression were analyzed using qRT-PCR and microarray transcriptome analysis.

Main Results:

  • PR-PFD treatment significantly reduced the elevated hepatic expression of miR-21a-5p, miR-34a-5p, miR-122-5p, and miR-103-3p in MAFLD/NASH mice.
  • Transcriptome analysis revealed downregulation of 52 genes involved in lipid biosynthesis, collagen synthesis, and inflammatory response in the PR-PFD treated group.
  • PR-PFD administration reversed the modifications in gene metabolic pathways associated with lipid metabolism, inflammation, and insulin resistance observed in MAFLD/NASH animals.

Conclusions:

  • PR-PFD demonstrates therapeutic potential in modulating key miRNAs and reversing detrimental gene expression changes in MAFLD/NASH.
  • These findings suggest PR-PFD as a promising agent for managing MAFLD/NASH by targeting molecular pathways involved in liver injury and metabolic dysfunction.

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