LncRNA Gm12840 mediates WISP1 to regulate ischemia-reperfusion-induced renal fibrosis by sponging miR-677-5p

Epigenomics. 2020 Dec;12(24):2205-2218. doi: 10.2217/epi-2020-0054. Epub 2020 Dec 22.

Abstract

Aim: We aimed to identify that long noncoding RNAs (lncRNAs) are involved in ischemia-reperfusion (IR)-induced late fibrosis of kidney and may constitute novel therapeutic strategies for acute kidney injury-induced chronic kidney disease. Materials & methods: We performed the mouse model of IR later induced renal fibrosis and analyzed lncRNA profiles using second-generation sequencing during the pathogenesis. Results: The expression levels of 43 lncRNAs and 141 lncRNAs were respectively changed significantly 7 days and 2 weeks after IR treatment. Based on the correlation analysis of the differentially expressed genes, the interaction networks of lncRNAs, miRNAs and mRNA were structured. Conclusion: LncRNA (Gm12840) could act as a sponge for miR-677-5p to mediate fibroblast activation induced by TGF-β1 via the WISP1/PKB (Akt) signaling pathway.

Keywords: fibrosis; ischemia; lncRNA; renal; reperfusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / etiology
  • Animals
  • CCN Intercellular Signaling Proteins / genetics*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibrosis
  • Gene Expression Regulation*
  • HEK293 Cells
  • Humans
  • Kidney / metabolism*
  • Kidney / pathology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / metabolism
  • NIH 3T3 Cells
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Long Noncoding / metabolism*
  • RNA, Messenger / metabolism
  • Reperfusion Injury / complications
  • Signal Transduction
  • Transforming Growth Factor beta1 / pharmacology

Substances

  • CCN Intercellular Signaling Proteins
  • CCN4 protein, mouse
  • MicroRNAs
  • Proto-Oncogene Proteins
  • RNA, Long Noncoding
  • RNA, Messenger
  • Transforming Growth Factor beta1
  • Proto-Oncogene Proteins c-akt