Circulating Fibroblast Growth Factor-2 precipitates HIV-nephropathy in mice.

Disease Models & Mechanisms
Jharna R DasPatricio E Ray

Abstract

Over 80% of all children living with HIV reside in Africa and are at risk of developing HIV-associated nephropathy (HIVAN). Once HIVAN is established in children, it is difficult to revert its progression to chronic kidney failure even using antiretroviral drugs. Therefore, new therapeutic strategies are needed. Previous studies showed that the risk of developing HIVAN increases in children with high circulating levels of FGF-2, but it is unclear whether FGF-2 per se precipitates HIVAN. To unravel the role of circulating FGF-2 in childhood HIVAN, we used the HIV-Tg26 mouse model of HIVAN. Briefly, we demonstrated that circulating FGF-2 was preferentially recruited in the kidney of HIV-Tg26 mice with renal disease, and precipitated HIVAN in young mice without pre-existing kidney disease by activating the pERK pathway in renal epithelial cells without previously inducing the expression of HIV-1 genes. Wild type mice injected with recombinant adenoviral FGF-2 vectors (rAd-FGF-2) carrying a secreted form of human FGF-2 developed transient and reversible HIVAN-like lesions, including proteinuria and glomerular enlargement. HIV-Tg26 mice injected with rAd-FGF-2 developed more significant proliferative and pro-fibrotic inflammatory le...Continue Reading

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