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Kidney Week

Abstract: PO2445

Major Vault Protein Promotes Macrophage-to-Myofibroblast Transition and Tubulointerstitial Fibrosis in a Murine Model of CKD

Session Information

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Wong, Cheuk Yin, Department of Medicine, the University of Hong Kong, Hong Kong, Hong Kong
  • Yung, Susan, Department of Medicine, the University of Hong Kong, Hong Kong, Hong Kong
  • Chan, Caleb C-Y, Department of Medicine, the University of Hong Kong, Hong Kong, Hong Kong
  • Chan, Tak Mao Daniel, Department of Medicine, the University of Hong Kong, Hong Kong, Hong Kong
Background

Chronic kidney disease (CKD) is characterized by progressive interstitial fibrosis and tubular atrophy, and inflammatory cell infiltration. We found that major vault protein (MVP), a key component of the vault complex, contributed to increased matrix protein deposition in an adenine-induced murine CKD model. We continued to investigate whether MVP contributes to interstitial fibrosis.

Methods

CKD was induced in MVP wild-type (WT) and knockout (KO) mice by feeding with casein-based chow containing 0.2% adenine for 8 weeks, and mice were sacrificed and renal cortical tissue harvested for qPCR, immunohistochemistry and flow cytometry analysis. Mice fed casein-based chow served as controls.

Results

MVP WT mice with CKD showed increased MVP mRNA compared to control WT mice. In MVP WT mice with CKD there was increased macrophage infiltration in the tubulo-interstitium that co-localized with collagen I, fibronectin and a-smooth muscle actin, suggesting macrophage-to-myofibroblast transition. Flow cytometric data showed increased CD45+ cells and F4/80+ / CD11b+ macrophages in MVP WT mice with CKD. MVP KO mice with CKD showed reduced infiltration of macrophages in the tubulo-interstitium, with lower transition to myofibroblasts (P<0.01); and there was decreased MCP-1, MCP-1 receptor and TNF-a mRNA expression, with better preservation of normal renal histology.

Conclusion

The findings suggest that MVP may contribute to the pathogenesis of CKD by promoting macrophage infiltration and their transition to myofibroblasts.

Funding

  • Government Support – Non-U.S.