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. 2022 Apr;395(4):445-458.
doi: 10.1007/s00210-022-02208-4. Epub 2022 Feb 4.

Alteration of N6-methyladenosine epitranscriptome profile in lipopolysaccharide-induced mouse mesangial cells

Tao Liu  1   2 , Xing Xing Zhuang  2   3 , Xiu Juan Qin  1 , Liang Bing Wei  1 , Jia Rong Gao  4   5
Affiliations

Alteration of N6-methyladenosine epitranscriptome profile in lipopolysaccharide-induced mouse mesangial cells

Tao Liu et al. Naunyn Schmiedebergs Arch Pharmacol. 2022 Apr.

Abstract

N6-Methyladenosine (m6A) is the most prevalent internal modification of messenger RNA (mRNA) in eukaryotes. The underlying molecular mechanisms of m6A modification in chronic glomerulonephritis (CGN) remain unexplored. Here, we performed methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) analyses to assess the alterations of epitranscriptome-wide m6A profile in lipopolysaccharide (LPS)-induced mouse mesangial cells (MMC). The results of our data showed 2153 significantly differential m6A peaks and 358 significantly differentially expressed genes. Furthermore, integrated analysis from MeRIP-seq and RNA-seq identified a total of 64 genes with differential m6A modification and expressed levels, of which 5 genes displayed hypermethylation and upregulation, 42 genes displayed hypermethylation and downregulation, 11 genes displayed hypomethylation and upregulation, and 8 genes displayed hypomethylation and downregulation. Many of them (including Fosl1, Sorbs1, Ambp, Fgfr3, Nedd9, Fgg, Trim13, Fgf22, Mylk, and Muc6) are implicated in the regulation of the immune and inflammatory response. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis found that differential 64 genes were mainly enriched in fatty acid oxidation, apoptosis signaling pathway, complement and coagulation cascades, and PPAR signaling pathway. Together, our study provided a new perspective on the understanding of molecular features of m6A modification in CGN pathogenic pathogenesis.

Keywords: Chronic glomerulonephritics; MMC cells; RNA-seq; m6A methylation; m6A-seq.

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