ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Please note that you are viewing an archived section from 2019 and some content may be unavailable. To unlock all content for 2019, please visit the archives.

Abstract: TH-PO497

Protective Role of Kallistatin Against Renal Fibrosis in Unilateral Ureteral Obstruction

Session Information

  • 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).