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

Increasing evidence has revealed a close relationship between circular RNAs (circRNAs) and the regulatory process of cell aging. 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_012707 in renal aging.High-throughput sequencing was performed to detect the differential expression of circRNAs in kidney tissues of the old and young 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. SA-ß-Gal, Masson Assay is used to evaluate the role of hsa_circ_0127071 in the aging process of kidney tissue.Using RIP, RNA pull down, and 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. The activity of JAK2/STAT5 signaling pathway was decreased after silencing EIF4A3, which could delay the aging process. On the basis of silencing EIF4A3 expression, the JAK2/STAT5 signaling pathway was activated by EPO processing, and the senescence of HGMCs increased. After treatment with LOS, the activity of JAK2/STAT5 pathway was decreased and the aging process of HGMCs was delayed. Our findings showed that hsa_circ_0127071 promoted renal aging, and confirmed the regulatory role of EIF4A3/hsa_circ_0127071/JAK2/STAT5 in the regulation of renal aging, providing a new therapeutic target for drug design and early diagnosis. Overall design: In conclusion, this study intends to use human kidney tissues and human mesangial cells for validation experiments through transcriptional gene assay, KEGG pathway and other prediction, aiming to explore that EIF4A3-induced hsa_circ_0127071 promotes human glomerular mesangial cells senescence via JAK2/STAT5 signaling pathway. in order to provide a new therapeutic target for the prevention and treatment of renal aging.