Alteration of N⁶-Methyladenosine Epitranscriptome Profile in Unilateral Ureteral Obstructive Nephropathy

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::

• mRNA
• N⁶-methyladenosine (m⁶A)
• obstructive nephropathy
• renal interstitial fibrosis
• unilateral ureteral obstruction (UUO)

Financial & competing interests disclosure

This research was partly funded by National Natural Science Foundation of China (no. 81571514) and 345 Talent Project of Shengjing Hospital of China Medical University. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that the animal procedures used in this study were approved by the Medical Research and New Technology Ethics Committee of Shengjing Hospital of China Medical University (no. 2018PS229K). All experiments were performed in accordance with the National Institute of Health Guide for the care and use of laboratory animals. The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations.

Additional information

Funding

This research was partly funded by National Natural Science Foundation of China (no. 81571514) and 345 Talent Project of Shengjing Hospital of China Medical University. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.