Abstract: FR-PO394
DcR2 Interacts with Peroxiredoxin 1 and Accelerates Senescence of Renal Tubular Epithelial Cell in Diabetic Nephropathy
Session Information
- Diabetic Kidney Disease: Basic - II
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- Chen, Jia, Daping Hospital, Chongqing, China
- He, Yani, Daping Hospital, Chongqing, China
Background
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD). The extent of tubulointerstitial lesions ultimate determines the rate of attrition of renal function, and premature senescence of RTECis a prominent renal histological change in DN. Decoy receptor 2 (DcR2) is a transmembrane receptor of cellular senescent marker, but the interaction proteins and the role of DcR2 are not clear.
Methods
139 DN patients which diagnosed by renal biopsy were enrolled. Renal DcR2 and senescent markers,P16 and SA-β-gal were detected with immunostaining. The degree of cell senescence were evaluated after regulation of DcR2 expression. Co-IP combining with LC-MS/MS were screened the interaction proteins for DcR2 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.
Results
DcR2 was primarily expressed in renal proximal tubules, and co-expression with senescent markers P16 and SA-β-gal. Overexpression of DcR2 accelerate whereas knockdown inhibited the expression of P16 and SA-β-gal. Quantitative proteomics identified 135 differentially expressed proteins (DEPs) in renal tissue and 59 DEPs in HG. Peroxiredoxin 1 (PRDX1), an enzyme of oxidative stress, was screened not only in renal tissue but also in HG-induced cells. The interaction of DcR2 and PRDX1 was verified in vivo and in vitro. DcR2 can inhibited the peroxidase activity of PRDX1 through promote the phosphorylation of PRDX1.
Conclusion
DcR2 accelerates tubular cell senescence through interacting with a new partner PRDX1, and DcR2 can affect the peroxidase activity of PRDX1 through regulating the phosphorylation of PRDX1 in DN.
Funding
- Government Support - Non-U.S.