LncRNA Gm44981 modulates EZH2–H3K27me3–p21 axis to suppress mesangial cell senescence and kidney aging

Aging imposes significant influence in alteration of organ structure, function, and susceptibility to disease. Long non-coding RNAs (lncRNAs) are frequently dysregulated in the aging kidney, however, the key lncRNAs and associated mechanism involved in regulating kidney aging remains poorly investigated. Herein, we performed unbiased whole transcriptome sequencing on the kidney tissue samples from young and aging mice. The results of differentially expressed lncRNAs among two groups revealed that Gm44981, a 1943 bp lncRNA, was down regulated in the aging kidney. Fluorescence in situ hybridization (FISH) assay showed that Gm44981 was mainly located in the nucleus of glomerular mesangial cells (MCs). Functional experiments showed that overexpression of Gm44981 in MC cells significantly promoted cell proliferation capacity. Specifically, overexpression of Gm44981 was associated with increased H3K27me3 level and enhanced enrichment of EZH2 at the Cdkn1a promoter region, which correlated with the suppression of Cdkn1a expression and attenuated MCs senescence. Together, our findings highlighted the crucial roles of lncRNA Gm44981 in regulation of glomerular MCs senescence and provided novel targets for aging therapy.