METTL3 alleviates D-gal-induced renal tubular epithelial cellular senescence via promoting miR-181a maturation

Mechanisms of Ageing and Development(2023)

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摘要
Methyltransferase-like protein 3 (METTL3) mediated N6-Methyladenosine (m6A) modification has been implicated in many physiological and pathological processes. However, its function and mechanism in kidney aging are not entirely clear. Here, we investigated changes in m6A levels of aging kidneys and the role of METTL3 in senescent renal tubular epithelial cells and its potential mechanisms. First, we used the naturally aged mouse model and the D-galactose (D-gal)-induced aged mouse model. Dot blot and m6A RNA methylation quantification showed significantly decreased m6A levels in both models. In addition, we observed that METTL3 was down-regulated in D-gal-induced senescent human renal tubular epithelial cell line (HK-2). METTL3 reduction was associated with senescence-related phenotypes of HK-2 cells. We also found that miR-181a-5p attenuated HK-2 senescence by targeting the NF-κB pathway. Moreover, METTL3 was able to promote the maturation of miR-181a-5p and then inhibited the expression of NF-κB and IL-1α. Taken together, we demonstrate that the METTL3/miR-181a-5p/NF-κB axis counteracts HK-2 senescence. Our results suggest that METTL3 may be a novel biomarker and a potential therapy target for kidney aging.
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METTL3,m6A,D-gal,HK-2,SA-β-gal,PBMCs,MTC,MB,miRNAs,SASP
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