FTO overexpression expedites wound healing and alleviates depression in burn rats through facilitating keratinocyte migration and angiogenesis via mediating TFPI-2 demethylation

Background Abnormal methylation of N6-methyladenosine (m6A) is reportedly associated with central nervous system disorders. However, the role of m6A mRNA methylation in unconjugated bilirubin (UCB) neurotoxicity requires further research. Methods Rat pheochromocytoma PC12 cells treated with UCB were used as in vitro models. After the PC12 cells were treated with UCB (0, 12, 18, and 24 µM) for 24 h, the total RNA m6A levels were measured using an m6A RNA methylation quantification kit. The expression of m6A demethylases and methyltransferases was detected through western blotting. We determined the m6A mRNA methylation profile in PC12 cells exposed to UCB (0 and 18 µM) for 24 h using methylated RNA immunoprecipitation sequencing (MeRIP-seq). Results Compared with the control group, UCB (18 and 24 µM) treatment decreased the expression of the m6A demethylase ALKBH5 and increased the expression of the methyltransferases METTL3 and METTL14, which resulted in an increase in the total m6A levels in PC12 cells. Furthermore, 1533 m6A peaks were significantly elevated and 1331 peaks were reduced in the UCB (18 µM)-treated groups compared with those in the control group. Genes with differential m6A peaks were mainly enriched in protein processing in the endoplasmic reticulum, ubiquitin-mediated proteolysis, cell cycle, and endocytosis. Through combined analysis of the MeRIP-seq and RNA sequencing data, 129 genes with differentially methylated m6A peaks and differentially expressed mRNA levels were identified. Conclusion Our study suggests that the modulation of m6A methylation modifications plays a significant role in UCB neurotoxicity.

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Expression profiling of N6-methyladenosine-modified mRNA in PC12 cells in response to unconjugated bilirubin

Zhou

Liao

Zhang

et al. 2023

Mol Biol Rep

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The potential role of RNA modification in skin diseases, as well as the recent advances in its detection methods and therapeutic agents

Yu,

Liang,

Wang

et al. 2023

Biomedicine & Pharmacotherapy

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The N6-methyladenosine modification in pathologic angiogenesis

Li,

Xuan,

Yin

et al. 2024

Life Sciences

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FTO overexpression expedites wound healing and alleviates depression in burn rats through facilitating keratinocyte migration and angiogenesis via mediating TFPI-2 demethylation

Cited by 8 publications

References 32 publications

Expression profiling of N6-methyladenosine-modified mRNA in PC12 cells in response to unconjugated bilirubin

Expression profiling of N6-methyladenosine-modified mRNA in PC12 cells in response to unconjugated bilirubin

The potential role of RNA modification in skin diseases, as well as the recent advances in its detection methods and therapeutic agents

The N6-methyladenosine modification in pathologic angiogenesis

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