Go to The Journal of Clinical Investigation
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Immunology
    • Metabolism
    • Nephrology
    • Oncology
    • Pulmonology
    • All ...
  • Videos
  • Collections
    • Resource and Technical Advances
    • Clinical Medicine
    • Reviews
    • Editorials
    • Perspectives
    • Top read articles
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • In-Press Preview
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Transfers
  • Advertising
  • Job board
  • Contact
Loss of miR-141/200c ameliorates hepatic steatosis and inflammation by reprogramming multiple signaling pathways in NASH
Melanie Tran, … , Dong-Ju Shin, Li Wang
Melanie Tran, … , Dong-Ju Shin, Li Wang
Published November 2, 2017
Citation Information: JCI Insight. 2017;2(21):e96094. https://doi.org/10.1172/jci.insight.96094.
View: Text | PDF
Research Article Hepatology Inflammation

Loss of miR-141/200c ameliorates hepatic steatosis and inflammation by reprogramming multiple signaling pathways in NASH

  • Text
  • PDF
Abstract

Accumulation of lipid droplets and inflammatory cell infiltration is the hallmark of nonalcoholic steatohepatitis (NASH). The roles of noncoding RNAs in NASH are less known. We aim to elucidate the function of miR-141/200c in diet-induced NASH. WT and miR-141/200c–/– mice were fed a methionine and choline deficient (MCD) diet for 2 weeks to assess markers of steatosis, liver injury, and inflammation. Hepatic miR-141 and miR-200c RNA levels were highly induced in human patients with NASH fatty liver and in WT MCD mice. miR-141/200c–/– MCD mice had reduced liver weights and triglyceride (TG) levels, which was associated with increased microsomal TG transfer protein (MTTP) and PPARα but reduced SREBP1c and FAS expression. Inflammation was attenuated and F4/80 macrophage activation was suppressed in miR-141/200c–/– mice, as evidenced by decreased serum aminotransferases and IL-6 and reduced hepatic proinflammatory, neutrophil, and profibrotic genes. Treatment with LPS in BM-derived macrophages isolated from miR-200c/141–/– mice polarized macrophages toward the M2 antiinflammatory state by increasing Arg1 and IL-10 levels while decreasing the M1 marker iNOS. In addition, elevated phosphorylated AMPK (p-AMPK), p-AKT, and p-GSK3β and diminished TLR4 and p-mTOR/p-4EBP1 proteins were observed. Lipidomics and metabolomics revealed alterations of TG and phosphatidylcholine (PC) lipid species by miR-141/200c deficiency. In summary, miR-141/200c deficiency diminished NASH-associated hepatic steatosis and inflammation by reprogramming lipid and inflammation signaling pathways.

Authors

Melanie Tran, Sang-Min Lee, Dong-Ju Shin, Li Wang

×

Figure 1

Levels of miR-141/200c are increased in steatotic livers of patients and mice with NASH.

Options: View larger image (or click on image) Download as PowerPoint
Levels of miR-141/200c are increased in steatotic livers of patients and...
(A) qPCR analysis of miR-141 and miR-200c expression in human liver specimens (n = 10–20 samples per group). (B) qPCR analysis of miR-141 and miR-200c expression in livers of WT mice fed the control diet (CD) and methionine and choline–deficient (MCD) diet (n = 5–7 mice per group). (C) Targeting strategy for generating miR-141/200c–double KO mice. (D) qPCR analysis of miR-141 and miR-200c expression in livers of miR-141/200c–/– mice and their WT littermates (n = 5 mice per group). Data are represented as mean ± SEM. Differences between 2 groups were compared using a Student’s unpaired t test. For multiple groups, differences were compared using a one-way ANOVA followed by Newman-Keuls multiple comparisons test. **P < 0.01 indicate statistical significance.

Copyright © 2023 American Society for Clinical Investigation
ISSN 2379-3708

Sign up for email alerts