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Abstract: TH-OR064

DcR2 Mediates Senescent Phenotype of Tubular Cell by Interacting with PRDX1: A Novel Mechanism of Renal Fibrosis in Diabetic Nephropathy

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic


  • Chen, Jia, Daping hospital, Chongqing, Chongqing, China
  • He, Yani, Daping hospital, Chongqing, Chongqing, China

Premature senescence of renal tubular epithelial cell (RTEC), which is involved in renal fibrosis, is a key event in the progression of DN. However, the underlying mechanism remains unclear. Our study investigated the role of Decoy receptor DcR2 in renal fibrosis and explored the mechanism of DcR2 mediated the senescent phenotype of RTEC.


215 DN patients which diagnosed by renal biopsy were enrolled. Renal DcR2 and senescent markers, P16 and SA-β-gal were detected with confocal immunostaining. The degree of renal fibrosis and cell senescence were evaluated after regulation of DcR2 expression in vivo and vitro. Co-IP combining with LC-MS/MS were screened the DcR2-interaction proteins in renal tissue and high glucose (HG) induced-proximal tubular epithelial cells (PTECs). The interaction of DcR2 and PRDX1 was detected by Co-IP and pull down assay. Peroxidase activity of PRDX1 was assessed by the kits of ROS and specific 2-cys peroxidase activity. The level of PRDX1 phosphorylation was detected through WB.


DcR2 was high specifically expressed in RTEC and associated with renal fibrosis. Confocal analysis indicated DcR2 co-expressed with senescent markers in the development of DN. Knockdown of DcR2 effectively decreased renal fibrosis and alleviated renal function in streptozotocin (STZ)-induced DN mice. Furthermore, DcR2 knockdown significantly inhibited RTEC senescence and promoted the secretion of senescence-associated secretory phenotype (SASP), such as IL-1β, MMP-2 and TGF-β1. However, DcR2 overexpression showed the opposite effects. In vivo and vitro studies revealed that DcR2 interacts with peroxiredoxin 1 (PRDX1) using quantitative proteomics, which have peroxidase and antioxidant activity in cytoplasm. Following study indicated PRDX1 was co-expressed with senescent phenotype, and PRDX1 knockdown accelerated whereas overexpression inhibited RTEC senescent phenotype. The interaction of DcR2-PRDX1 mediated RTEC senescent phenotype. Moreover, DcR2 inhibited the peroxidase activity of PRDX1 resulting in oxidative stress through promoting PRDX1 phosphorylation.


DcR2 interacts with PRDX1 and aggravates renal fibrosis by mediating RTEC senescent phenotype, suggesting DcR2 as a potential therapeutic target for the amelioration of DN progression.


  • Government Support - Non-U.S.