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

Authors
  • Escutia-Gutiérrez, Rebeca1
  • Rodríguez-Sanabria, J. Samael1
  • Monraz-Méndez, C. Alejandra1
  • García-Bañuelos, Jesús1
  • Santos-García, Arturo2
  • Sandoval-Rodríguez, Ana1, 3
  • Armendáriz-Borunda, Juan1, 2, 3
  • 1 Health Sciences University Center, University of Guadalajara, Guadalajara, Jalisco, Mexico , Guadalajara (Mexico)
  • 2 School of Medicine and Health Sciences, Zapopan, Jalisco, Mexico , Zapopan (Mexico)
  • 3 CUCS, University of Guadalajara, 950 Sierra Mojada, Guadalajara, 44340, Mexico , Guadalajara (Mexico)
Type
Published Article
Journal
Scientific Reports
Publisher
Springer Nature
Publication Date
Jun 03, 2021
Volume
11
Issue
1
Identifiers
DOI: 10.1038/s41598-021-91187-2
Source
Springer Nature
License
Green

Abstract

miRNAs are involved in the development of metabolic associated fatty liver disease (MAFLD) and nonalcoholic steatohepatitis (NASH). We aimed to evaluate modifications by prolonged-release pirfenidone (PR-PFD) on key hepatic miRNAs expression in a MAFLD/NASH model. First, male C57BL/6J mice were randomly assigned into groups and fed with conventional diet (CVD) or high fat and carbohydrate diet (HFD) for 16 weeks. At the end of the eighth week, HFD mice were divided in two and only one half was treated with 300 mg/kg/day of PR-PFD mixed with food. Hepatic expression of miRNAs and target genes that participate in inflammation and lipid metabolism was determined by qRT-PCR and transcriptome by microarrays. Increased hepatic expression of miR-21a-5p, miR-34a-5p, miR-122-5p and miR-103-3p in MAFLD/NASH animals was reduced with PR-PFD. Transcriptome analysis showed that 52 genes involved in lipid and collagen biosynthesis and inflammatory response were downregulated in PR-PFD group. The expression of Il1b, Tnfa, Il6, Tgfb1, Col1a1, and Srebf1 were decreased in PR-PFD treated animals. MAFLD/NASH animals compared to CVD group showed modifications in gene metabolic pathways implicated in lipid metabolic process, inflammatory response and insulin resistance; PR-PFD reversed these modifications.

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