EIF4A3-induced hsa_circ_0127071 promotes human glomerular mesangial cells senescence via JAK2/STAT5 signaling pathway

Abstract

Abstract Circular RNAs (circRNAs) have garnered attention for their potential involvement in the regulation of cellular aging processes. Exploring the role and mechanism of circRNAs in cellular senescence may help to identify new anti-aging therapeutic targets. In the present study, we investigated the role and regulatory mechanism of hsa_circ_0127071 in renal aging. We employed high-throughput sequencing to assess circRNA expression differences in kidney tissues from young and old groups. qRT-PCR confirmed that the expression of hsa_circ_0127071 in kidney tissue of the old group was significantly higher than that of the young group. Cellular senescence was evaluated using SA-β-Gal staining and Masson’s trichrome staining. Using RNA Immunoprecipitation (RIP), RNA Pull-Down Assay (RNA pull down), and Western Blot (WB) to study the interaction between hsa_circ_0127071 and aging related pathway proteins. In this study, we found that the expression of hsa_circ_0127071 in kidney tissue of the old group was significantly higher than that of the young group. Silencing of EIF4A3, a protein involved in the JAK2/STAT5 signaling pathway, was found to delay the aging process. On the basis of silencing EIF4A3 expression, the JAK2/STAT5 signaling pathway was activated by Erythropoietin (EPO) processing, and the senescence of Human glomerular mesangial cells (HGMCs) increased. After treatment with Losartan (LOS), the activity of JAK2/STAT5 pathway was decreased and the aging process of HGMCs was delayed. Our findings demonstrate that hsa_circ_0127071 promotes renal aging through the EIF4A3/JAK2/STAT5 signaling axis, highlighting a novel potential therapeutic target for the management of renal aging and associated disorders.

Keywords

• Human glomerular mesangial cells
• Signaling pathway
• Renal aging
• Regulatory mechanism