2. Academic Validation
  3. IRF8 and RUNX1 cooperatively regulate the senescence and damage of urine-derived renal progenitor cells by upregulating LINC01806

IRF8 and RUNX1 cooperatively regulate the senescence and damage of urine-derived renal progenitor cells by upregulating LINC01806

  • Biochem Pharmacol. 2025 Jun 24:240:117068. doi: 10.1016/j.bcp.2025.117068.
Jie Ma 1,  Wei Yang 2,  Fu-Ming Chen 1,  Qian He 3,  Hua-Lin Ma 4,  Cong-Hui Li 4,  Min-Li Liang 1,  Jia-Qi Zhong 1,  Xin-Zhou Zhang 4,  Fu-Rong Li 5
Affiliations

Affiliations

  • 1 Translational Medicine Collaborative Innovation Center, The First Affiliated Hospital (Shenzhen People's Hospital), Southern University of Science and Technology, Shenzhen 518055, China; Guangdong Engineering Technology Research Center of Stem Cell and Cell Therapy, Shenzhen Key Laboratory of Stem Cell Research and Clinical Transformation, Shenzhen Immune Cell Therapy Public Service Platform, Shenzhen 518020, China.
  • 2 Guangdong Engineering Technology Research Center of Stem Cell and Cell Therapy, Shenzhen Key Laboratory of Stem Cell Research and Clinical Transformation, Shenzhen Immune Cell Therapy Public Service Platform, Shenzhen 518020, China; Shenzhen Salus BioMed Inc Ltd., Shenzhen, Guangdong, China.
  • 3 Guangdong Engineering Technology Research Center of Stem Cell and Cell Therapy, Shenzhen Key Laboratory of Stem Cell Research and Clinical Transformation, Shenzhen Immune Cell Therapy Public Service Platform, Shenzhen 518020, China; School of Food and Drug, Shenzhen Polytechnic University, Shenzhen 518055, China.
  • 4 Department of Nephrology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020 Guangdong, China.
  • 5 Translational Medicine Collaborative Innovation Center, The First Affiliated Hospital (Shenzhen People's Hospital), Southern University of Science and Technology, Shenzhen 518055, China; Guangdong Engineering Technology Research Center of Stem Cell and Cell Therapy, Shenzhen Key Laboratory of Stem Cell Research and Clinical Transformation, Shenzhen Immune Cell Therapy Public Service Platform, Shenzhen 518020, China; Institute of Health Medicine, Southern University of Science and Technology, Shenzhen 518055, China. Electronic address: lifurong@mail.sustech.edu.cn.
PMID: 40571211 DOI: 10.1016/j.bcp.2025.117068
Abstract

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.

Keywords

Chronic kidney disease; LINC01806; SASP; Senescence; Urine-derived renal progenitor cells.

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