Podocyte Participates in the ST2 Related Renal Fibrosis.
1Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
2Seoul National University Biomedical Research Institute, Seoul, Republic of Korea
3Kidney Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
4Internal Medicine, National Medical Center, Seoul, Republic of Korea
5Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Republic of Korea
Meeting: 2017 American Transplant Congress
Abstract number: 314
Keywords: Fibrosis, Renal failure
Session Information
Date: Monday, May 1, 2017
Session Name: Concurrent Session: Basic Chronic Rejection
Session Time: 4:30pm-6:00pm
Presentation Time: 5:18pm-5:30pm
Location: E351
Objective Soluble ST2 (sST2) which is the receptor of IL-33 is involved in renal inflammation and it is also correlated with disease severity in chronic kidney disease (CKD). Here, we report the ameliorating effect of the ST2 blockade as well as the role of sST2 in the progression renal fibrosis.
Methods Serum and urine levels of sST2 were measured by ELISA in 143 CKD patients. And ST2 mRNA levels were quantified in blood and urine cells. Immunohistochemistry (IHC) stain of ST2 was performed in kidney biopsy samples of CKD patients. Further, urine cells were co-stained with podocalyxin and ST2 to characterize the cell type.And fibrosis induced by TGF-beta in primary cultured podocytes was evaluated with fibronectin, IL-33 and ST2 mRNA expressions. Anti-ST2 monoclonal antibody was treated to evaluate the neutralizing effect of ST2 on renal fibrosis.
Results Serum (P = 0.002) and urine (P < 0.001) sST2 levels significantly increased as renal function deteriorates. Urine sST2 level adjusted by urine creatinine showed the same pattern. (P < 0.001) Serum (P = 0.023) and urine (P = 0.03) ST2 mRNA expressions were elevated in CKD stage 5 patients compared with other CKD stages. ST2 IHC stain in CKD stage 5 showed 3-fold increase than CKD stage 1. A large portion of urine cells were ST2-rich podocytes and the proportion of podocytes increased as renal function decreases, when we performed flow-cytometry using CD31 and podocalyxin antibody.When the patients were subdivided by 0.5 g/g proteinuria, patients with more proteinuria had a high concentration of urine ST2. (P = 0.02) After fibrosis induction in primary cultured podocytes, mRNA and protein expressions of fibronectin, IL-33 and ST2 showed positive correlation with the fibrosis severity. And anti-ST2 dose-dependently reduced the fibrosis.
Conclusion Elevated serum and urine sST2 levels are associated with the progression of CKD and podocytes involved in this process. ST2-mediated IL-33 signaling may have a considerable role in the progression renal dysfunction. And ST2 blockade is a potential therapeutic target for renal preservation.
CITATION INFORMATION: Kim Y, Yang S, Cha R, Yu M.-Y, Lee S, Lee H, Lee J, Kim D, Kim S, Kim Y. Podocyte Participates in the ST2 Related Renal Fibrosis. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Kim Y, Yang S, Cha R, Yu M-Y, Lee S, Lee H, Lee J, Kim D, Kim S, Kim Y. Podocyte Participates in the ST2 Related Renal Fibrosis. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/podocyte-participates-in-the-st2-related-renal-fibrosis/. Accessed December 13, 2019.« Back to 2017 American Transplant Congress