LncRNA OIP5-AS1 Promotes Glomerular Mesangial Cell Senescence by Interacting With ELAVL1 to Upregulate HMGB1

Glomerular mesangial cell (GMC) senescence contributes to the progression of various age-related kidney diseases. However, the molecular mechanisms driving GMC aging remain poorly understood. OIP5-AS1, a long non-coding RNA (lncRNA), has been implicated in cellular senescence in other systems, but its role in renal aging remains unclear. This work aimed to elucidate the functional role and underlying mechanism of OIP5-AS1 in GMC senescence. A D-galactose (D-gal)-induced senescence model was established in both mouse kidneys and SV40-MES13 mesangial cells. RT-qPCR was performed to quantify the levels of OIP5-AS1, ELAVL1, and HMGB1, while CCK-8 assays assessed cellular metabolic activity. Cellular senescence was evaluated using SA-β-gal staining, and the expression of senescence-associated proteins (p16, p21, p53) was quantified by Western blot analysis. Levels of SASP-related cytokines, including IL-6, IL-1β, TNF-α, and IL-18, were measured via ELISA. To explore the underlying mechanism, RNA pull-down and RIP assays were performed to investigate the interactions among OIP5-AS1, ELAVL1, and HMGB1, while actinomycin D assays were used to evaluate HMGB1 mRNA stability. OIP5-AS1 expression was markedly elevated in renal tissues and GMCs following D-gal-induced senescence. Knockdown of OIP5-AS1 alleviated cellular senescence. Mechanistically, OIP5-AS1 directly interacted with ELAVL1, thereby stabilizing HMGB1 mRNA and promoting HMGB1 expression. Rescue experiments further confirmed that ELAVL1 and HMGB1 mediated OIP5-AS1-induced GMC senescence. LncRNA OIP5-AS1 promotes GMC senescence by interacting with ELAVL1 to upregulate HMGB1.