The role and mechanism of METTL1 in regulating the phenotype and function of renal macrophages

Macrophages promote the progression of acute kidney injury (AKI), but the specific factor that regulates their phenotype and function remains unknown. Preliminary experimental results indicate the following: 1) The level of METTL1 and its mediated m7G modification were significantly up-regulated in macrophages in AKI; 2) The absence of METTL1 in macrophages alleviated renal injuries in AKI mice; 3) METTL1 deficiency suppressed the proportions of pro-inflammatory macrophages in renal tissues. Based on these findings, we hypothesize that AKI increases the level of METTL1 and m7G modification in macrophages, promoting their differentiation into a pro-inflammatory phenotype and ultimately worsening kidney damage. This study aims to investigate the expression of METTL1 in macrophages in patients and mice with AKI. Myeloid METTL1 conditional knockout mice were utilized to elucidate the regulatory role of m7G modification in macrophage differentiation. Additionally, target genes with immunoregulatory functions of m7G modification in macrophages were identified through m7G sequencing and transcriptomics. This study will elucidate the novel mechanism which METTL1-mediated m7G modification regulates macrophage plasticity to promote AKI, and also lays the foundation for using METTL1 as a drug target to treat inflammatory diseases.