Animal models of fibrosis

UUO renal fibrosis model

This model is induced in mice or rats by unilateral ureteral ligation (UUO) of the left ureter. The animals rapidly develop, within a few days, severe tubulo-interstitial renal fibrosis with an inflammatory cell infiltrate in the affected kidney. This is an ideal “go or no-go” model to test the potential anti-fibrotic activity of (new) compounds.

References

Bascands, J. L. and Schanstra, J. P., Obstructive nephropathy: insights from genetically engineered animals. Kidney Int 2005

Klein, J., Gonzalez, J., Duchene, J., Esposito, L., et al., Delayed blockade of the kinin B1 receptor reduces renal inflammation and fibrosis in obstructive nephropathy. Faseb J 2009

Pradere, J. P., Klein, J., Gres, S., Guigne, C., et al., LPA1 receptor activation promotes renal interstitial fibrosis. J Am Soc Nephrol 2007

Schanstra, J. P., Neau, E., Drogoz, P., Arevalo Gomez, M. A., et al., In vivo bradykinin B2 receptor activation reduces renal fibrosis. J Clin Invest 2002

SNX renal fibrosis model

This model consists at reducing the renal mass by 83%. This induces hyperfiltration and induces over a period of around 6 months significant fibrotic lesions in mice (C57bl/6j). In rats the model is somewhat faster as it induces renal fibrosis in 3 months. This is thus a more chronic model of the development of fibrosis somewhat closer to what is observed in humans.

Reference

Schanstra, J. P., Bachvarova, M., Neau, E., Bascands, J. L. and Bachvarov, D., Gene expression profiling in the remnant kidney model of wild type and kinin B1 and B2 receptor knockout mice. Kidney Int 2007