IRF8 and RUNX1 cooperatively regulate the senescence and damage of urine-derived renal progenitor cells by...

Urine-derived renal progenitor cells (UdRPCs) from healthy individuals have been identified as having the potential to repair kidney damage. However, it remains uncertain whether UdRPCs retain their functionality in chronic kidney disease (CKD) patients. In this study, UdRPCs were isolated from healthy individuals and CKD patients. Notably, senescent cells were observed in the UdRPCs of CKD patients, which increase with the severity of CKD, hindering the repair of renal tissue damage and exacerbating the progression of CKD. This senescence phenotype is characterized by decreased proliferation, increased expression of kidney injury marker 1 (KIM-1), and an enhanced senescence-associated secretory phenotype (SASP). Transcriptomics analysis revealed a significant correlation between long intergenic non-coding RNA 01806 (LINC01806) and UdRPCs damage and senescence. LINC01806 activation modulates the expression of KIM-1 and senescence-related factors (p53, p21 and p16), promotes SASP secretion by stimulating the MAPK pathway, thereby inducing damage and senescence in UdRPCs. Mechanistically, the IRF8-RUNX1 complex binds to the promoter of LINC01806, promoting its expression in the nucleus. Our findings clarify the pathogenesis of CKD from a new perspective, and more importantly, provide new targets for drug screening and potential therapeutic interventions.