Abstract: TH-PO497
Protective Role of Kallistatin Against Renal Fibrosis in Unilateral Ureteral Obstruction
Session Information
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CKD: Mechanisms - I
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Authors
- Yiu, Wai Han, The University of Hong Kong, Hong Kong, China
- Li, Ye, The University of Hong Kong, Hong Kong, China
- Lok, Sarah W.Y., The University of Hong Kong, Hong Kong, China
- Liu, Wing han, The University of Hong Kong, Hong Kong, China
- Chan, Loretta Y.Y., The University of Hong Kong, Hong Kong, China
- Leung, Joseph C K, The University of Hong Kong, Hong Kong, China
- Lai, Kar Neng, The University of Hong Kong, Hong Kong, China
- Lan, Hui Y., The Chinese University of Hong Kong, Shatin, Hong KOng, China
- Tang, Sydney C.W., The University of Hong Kong, Hong Kong, China
Background
Kallistatin is an endogenous serine protease inhibitor, which exerts anti-oxidative and anti-inflammatory function against kidney injury in animal models. However, it remains unknown whether kallistatin plays any protective effect in renal fibrosis, the final common pathway of all chronic kidney diseases.
Methods
Unilateral ureteral obstruction (UUO) was used to investigate the effect of kallistatin on renal extracellular matrix (ECM) protein expression and fibrotic signaling pathways. Renal kallistatin was either overexpressed by ultrasound-mediated microbubble kallistatin gene transfer or depleted by injection of anti-kallistatin antibody.
Results
Endogenous kallistatin expression was reduced in renal cortex of UUO kidneys. Kallistatin treatment significantly suppressed macrophage accumulation and the increase in ECM proteins including collagen type I and III as well as α-SMA. In contrast, injection with anti-kallistatin antibody aggravated renal fibrosis as evidenced by a further increase in ECM proteins. Moreover, depletion of endogenous kallistatin exacerbated UUO-induced Wnt4, β-catenin and Axin2 overexpression in the kidneys, while treatment with kallistatin reduced both Wnt4 and TGF-β over-expression in UUO kidneys.
Conclusion
Our results suggest a therapeutic role for kallistatin against renal fibrosis. Kallistatin exerts its anti-fibrotic effect in the kidney via modulating TGF-β and Wnt/β-catenin pathways, thereby offering a novel potential target of treatment for chronic kidney disease.
Fund support: Research Grants Council of Hong Kong (GRF grant number 17151716, CRF grant number C7018-16G), Hong Kong Society of Nephrology and Hong Kong Kidney Foundation Research Grant (2017).
