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Kidney Week

Abstract: PO2496

Blockade of Transglutaminase 2 Ameliorates CKD Progression

Session Information

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Moon, Jong joo, Seoul National University Biomedical Research Institute, Seoul, Korea (the Republic of)
  • Kwon, Soie, Seoul National University Hospital Department of Internal Medicine, Jongno-gu, Seoul, Korea (the Republic of)
  • Kim, Yong Chul, Seoul National University Hospital Department of Internal Medicine, Jongno-gu, Seoul, Korea (the Republic of)
  • Lee, Jae Wook, Division of Nephrology, Department of Internal Medicine, National Cancer Center, Goyang, Gyeonggi-do, Korea (the Republic of)
  • Kim, Dong Ki, Seoul National University Hospital Department of Internal Medicine, Jongno-gu, Seoul, Korea (the Republic of)
  • Kim, Yon Su, Seoul National University Hospital Department of Internal Medicine, Jongno-gu, Seoul, Korea (the Republic of)
  • Yang, Seung Hee, Kidney Research Institute, Seoul National University Medical Research Center, Seoul, Korea (the Republic of)
Background

Transglutaminase 2 (TG2) is a calcium dependent enzyme of the protein- glutamine γ-glutamyltransferases family that associated with fibrosis in CKD. The purpose of this study is to identify the relationship between expression of TG2 and the CKD progression in human kidney tissues, and to determine the biological activity of TG2 and TGFβ associated pathways in vitro and in vivo models.

Methods

We conducted immunohistochemistry staining of TG2 on kidney biopsy core derived from who were diagnosed chronic kidney disease. Plasma TG2 concentrations were measured by ELISA. Analyses were performed to reveal the relationship between TG2 and pathologic, functional markers of kidney disease. TG2 mRNA were evaluated at 3, 7, 14 days after from unilateral ureteral obstruction (UUO) mice model establishment with the fibrosis aggravation. To investigate the effect of TG2 inhibition on CKD progression, we used cystamine, well known TG2 inhibitor that induces the oxidation of vicinal cysteine residues of TG2 in primary cultured human tubular epithelial cells (hTECs) that injured with rTGFβ.

Results

Plasma TG2 concentrations showed positive relationships with CKD progression. Samples from progressed CKD patients showed higher plasma TG2 level. The tissue expression of TG2 were increased with CKD progression in human samples. After the establishment of the UUO model, elevation of TG2 mRNA levels were observed over time. TG2 inhibition by cystamine reduced 5.4% of apoptosis in hTECs that injured with rTGFβ (rTGFβ vs. rTGFβ+cystamine; 12.47% vs. 7.033%). Inhibiting TG2 using cystamine were associated with decreased fibronectin and increased E cadherin in rTGFβ inducted hTECs in a dose dependent manners.

Conclusion

The increased expression of TG2 were associated CKD progression in kidney. Suppressing TG2 activity could protect kidney cells from CKD deterioration through its anti-apoptotic and anti-fibrotic effect.