Alteration of N6-methyladenosine epitranscriptome profile in unilateral ureteral obstructive nephropathy

Epigenomics. 2020 Jul;12(14):1157-1173. doi: 10.2217/epi-2020-0126. Epub 2020 Jun 16.

Abstract

Aim: To reveal the alterations of N6-methyladenosine (m6A) epitranscriptome profile in kidney after unilateral ureteral obstruction in mice. Materials & methods: Total renal m6A and expressions of methyltransferases and demethylases were detected by colorimetric quantification method, real-time PCR and western blot, respectively. Methylated RNA immunoprecipitation sequencing was performed to map epitranscriptome-wide m6A profile. Results: Total m6A levels were time-dependent decreased within 1 week, with the lowest level detected at day 7. A total of 823 differentially methylated transcripts in 507 genes were identified. Specifically, demethylated mRNAs selectively acted on multiple pathways, including TGF-β and WNT. Conclusion: m6A modification has a functional importance in renal interstitial fibrosis during obstructive nephropathy and might be a promising therapeutic target.

Keywords: N6-methyladenosine (m6A); mRNA; obstructive nephropathy; renal interstitial fibrosis; unilateral ureteral obstruction (UUO).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / genetics
  • Animals
  • Blood Urea Nitrogen
  • Creatinine / blood
  • Epigenesis, Genetic*
  • Fibrosis
  • Kidney / pathology
  • Kidney Diseases / genetics*
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / genetics
  • Signal Transduction
  • Transcriptome*
  • Ureteral Obstruction / genetics*

Substances

  • RNA, Messenger
  • Creatinine
  • N-methyladenosine
  • Adenosine