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Research Paper|Volume 13, Issue 14|pp 18238—18256

Integrated analysis of m6A mRNA methylation in rats with monocrotaline-induced pulmonary arterial hypertension

Yunhong Zeng1,2, Ting Huang1,3, Wanyun Zuo4, Dan Wang2, Yonghui Xie1,2, Xun Wang2, Zhenghui Xiao5, Zhi Chen2, Qiming Liu4, Na Liu4, Yunbin Xiao2
  • 1Academy of Pediatrics, University of South China, Changsha 410007, China
  • 2Department of Cardiology, Hunan Children’s Hospital, Changsha 410007, China
  • 3Department of Utrasound, Hunan Children’s Hospital, Changsha 410007, China
  • 4Department of Cardiovascular Medicine, Second Xiangya Hospital, Central South University, Changsha 410011, China
  • 5Department of Intensive Care Unit, Hunan Children’s Hospital, Changsha 410007, China
* Equal contribution
Received: October 16, 2020Accepted: June 4, 2021Published: July 26, 2021
https://doi.org/10.18632/aging.203230

Copyright: © 2021 Zeng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: N6-methyladenosine (m6A) modification is one of the most common chemical modifications of eukaryotic mRNAs, which play an important role in tumors and cardiovascular disease through regulating mRNA stability, splicing and translation. However, the changes of m6A mRNA and m6A-related enzymes in pulmonary arterial hypertension (PAH) remain largely unexplored.

Methods: MeRIP-seq was used to identify m6A methylation in lung tissues from control and MCT-PAH rats. Western blot and immunofluorescence were used to evaluate expression of m6A-related enzymes.

Results: Compared with control group, m6A methylation was mainly increased in lung tissues from MCT-PAH rats. The up-methylated coding genes in MCT-PAH rats were primarily enriched in processes associated with inflammation, glycolysis, ECM-receptor interaction and PDGF signal pathway, while genes with down-methylation were enriched in processes associated with TGF-β family receptor members. The expression of FTO and ALKBH5 downregulated, METTL3 and YTHDF1 increased and other methylation modification-related proteins was not significantly changed in MCT-PAH rats lung tissues. Immunofluorescence indicated that expression of FTO decreased and YTHDF1 increased in small pulmonary arteries of MCT-PAH rats.

Conclusion: m6A levels and the expression of methylation-related enzymes were altered in PAH rats, in which FTO and YTHDF1 may play a crucial role in m6A modification.