Research Paper Volume 13, Issue 17 pp 21610—21627
Genome-wide identification of altered RNA m6A profiles in vascular tissue of septic rats
- 1 Department of Cardiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
- 2 Department of Physiology and Pathophysiology, Peking University School of Basic Medical Sciences, Beijing 100191, China
Received: February 22, 2021 Accepted: August 19, 2021 Published: September 10, 2021https://doi.org/10.18632/aging.203506
How to Cite
Copyright: © 2021 Shen 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.
Sepsis is the leading cause of death in hospital intensive care units. In light of recent studies showing that variations in N6-methyladenosine (m6A) levels in different RNA transcripts influence inflammatory responses, we evaluated the m6A profiles of rat aortic mRNAs and lncRNAs after lipopolysaccharide (LPS)-induced sepsis. LC-MS-based mRNA modification analysis showed that global m6A levels were significantly decreased in aortic tissue of rats injected intraperitoneally with LPS. This finding was consistent with downregulated expression of METTL3 and WTAP, two members of the m6A writer complex, in LPS-exposed aortas. Microarray analysis of m6A methylation indicated that 40 transcripts (31 mRNAs and 9 lncRNAs) were hypermethylated, while 223 transcripts (156 mRNAs and 67 lncRNAs) were hypomethylated, in aortic tissue from LPS-treated rats. On GO and KEGG analyses, ‘complement and coagulation cascades’, ‘transient receptor potential channels’, and ‘organic anion transmembrane transporter activity’ were the major biological processes modulated by the differentially m6A methylated mRNAs. In turn, competing endogenous RNA network analysis suggested that decreased m6A levels in lncRNA-XR_343955 may affect the inflammatory response through the cell adhesion molecule pathway. Our data suggest that therapeutic modulation of the cellular m6A machinery may be useful to preserve vascular integrity and function during sepsis.
m6A: N6-methyladenosine; lncRNAs: long non-coding RNAs; LPS: lipopolysaccharide; FTO: Fat mass and obesity-associated protein; METTL3: methyltransferase-like 3; ceRNA: Competing endogenous RNA; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; BP: biological process; CC: cellular component; MF: molecular function; YTHDF2: YT521-B homology domain family 2; VECs: vascular endothelial cells; VSMCs: vascular smooth muscle cells; TRP: transient receptor potential; TRPA1: TRP ankyrin 1; TRPV4: TRP vanilloid 4; DIC: disseminated intravascular coagulation; MALAT1: Metastasis-associated lung adenocarcinoma transcript 1.