Abstract: PO1710
Major Vault Protein Contributes to Increased Interstitial Fibrosis in a Murine Model of CKD
Session Information
- Glomerular Diseases: Fibrosis and Extracellular Matrix
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix
Authors
- Wong, Cheuk Yin, The University of Hong Kong, Hong Kong, Hong Kong
- Yung, Susan, The University of Hong Kong, Hong Kong, Hong Kong
- Chan, Caleb C-Y, The University of Hong Kong, Hong Kong, Hong Kong
- Chan, Tak Mao Daniel, The University of Hong Kong, Hong Kong, Hong Kong
Background
Chronic kidney disease (CKD) is a global health issue characterized by interstitial fibrosis and tubular atrophy, and progressive CKD results in kidney failure. There is currently no effective intervention for interstitial fibrosis. We previously showed that major vault protein (MVP), a key component of the vault complex, contributed to increased matrix protein deposition in murine unilateral ureteral obstruction (UUO) animal model. We extended our investigations to a murine model of CKD.
Methods
CKD was induced in MVP wild-type (WT) and knockout (KO) mice by feeding with standard chow containing 0.2% adenine for 8 weeks, after which time mice were sacrificed and kidneys were harvested and examined. Spot urine albumin-to-creatinine ratio was also measured. MVP WT and KO mice fed with standard chow served as controls.
Results
MVP WT mice with CKD showed increased MVP expression, predominantly in proximal tubular epithelial cells, compared to MVP WT control mice, and this was accompanied by development of proteinuria, tubular atrophy, tubulo-interstitial macrophage infiltration, and increased interstitial α-smooth muscle actin, fibronectin and collagen III expression. MVP KO mice with CKD showed less proteinuria (P<0.05) and less severe kidney histopathological features with reduced immune cell infiltration, and also reduced expression of fibrosis mediators compared to WT CKD mice. Exogenous TNF-α, IL-6, or MCP-1 increased MVP expression in cultured renal proximal tubular epithelial cells.
Conclusion
The data suggest that progressive CKD in this murine model is accompanied by increased renal tubular epithelial MVP expression, and MVP may contribute to the pathogenesis of tubulo-interstitial injury and damage.
Funding
- Government Support - Non-U.S.