Kidney Week

Abstract: SA-PO565

New Interaction between Galectin-3 and Cystinosin Reveals a Role of Inflammation in Kidney Pathogenesis in Cystinosis

Session Information

• Noncystic Mendelian Diseases
  November 04, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Genetic Diseases of the Kidney

• 801 Cystic Kidney Diseases

Authors

• Lobry, Tatiana Vm, UCSD, San Diego, California, United States

Tatiana Vm Lobry,

• Miller, Roy, UCSD, San Diego, California, United States

Roy Miller,

• Nevo, Nathalie, INSERM, Paris, France

Nathalie Nevo,

• Rocca, Celine, UCSD, San Diego, California, United States

Celine Rocca,

• Gubler, Marie-Claire, None, Paris, France

Marie-Claire Gubler,

• Montier, Tristan Y, Faculté de médecine de Brest, Brest, France

Tristan Y Montier,

• Antignac, Corinne, Imagine Institute, Paris, France

Corinne Antignac,

• Cherqui, Stephanie, University of California, San Diego, La Jolla, California, United States

Stephanie Cherqui,

Background

Cystinosis is a lysosomal storage disorder caused by mutations in the CTNS gene, encoding a lysosomal cystine transporter, leading to cystine accumulation. Affected individuals typically present with proximal tubulopathy, end-stage renal disease and multi-organ failure. Cystinosin has now been shown to have other cellular functions and an unbiased screen revealed a direct interaction of cystinosin with a member of the galectin’s family, galectin-3. This protein is implicated in different biological processes like cell death, cell cycle and inflammation.

Methods

We generated a murine model deficient for both cystinosin and galectin-3, the Ctns^-/-Gal3^-/- mice.

Results

We showed that cystinosin enhances galectin-3 lysosomal localization and degradation. In the Ctns^-/- mouse model, expression of galectin-3 was increased compared to wild-type. Moreover, absence of galectin-3 in cystinotic mice led to a better renal function and preservation of kidney morphology. Less inflammatory cell infiltration was observed in kidney of Ctns^-/-Gal3^-/- mice compared to Ctns^-/- mice, suggesting that galectin-3 mediated inflammation is involved in progression of the kidney disease in cystinosis.

Conclusion

We are currently investigating the mechanism by which galectin-3 induces recruitment of inflammatory cells in the kidney of cystinosis and we already found an interaction between galectin-3 and a chemokine implicated in the recruitment of monocytes/macrophages. This work brings new insights on the pathogenesis of the kidney disease in cystinosis and may lead to the identification of new drug targets to delay its progression to renal failure.

Funding

• NIDDK Support