Reduction of Stat3 activity attenuates HIV-induced kidney injury.

Published

Journal Article

HIV-1 Nef induces podocyte proliferation and dedifferentiation by activating the Stat3 and MAPK1,2 pathways. Activation of Stat3 also occurs in human kidneys affected by HIV-associated nephropathy (HIVAN), but its contribution to the development of HIVAN is unknown. Here, we generated HIV-1 transgenic mice (Tg26) with either 75% Stat3 activity (Tg26-SA/+) or 25% Stat3 activity (Tg26-SA/-). The kidneys of Tg26-SA/+ mice, but not Tg26-SA/- mice, showed increased Stat3 phosphorylation. The Tg26-SA/+ phenotype was not different from Tg26 mice, but Tg26-SA/- mice developed significantly less proteinuria, glomerulosclerosis, and tubulointerstitial injury. Tg26-SA/+ mice exhibited reduced expression of podocyte differentiation markers and increased expression of VEGF and proliferation markers as compared to Tg26-SA/- mice. Primary podocytes isolated from Tg26-SA/+ mice showed increased Stat3 phosphorylation and reduced expression of podocyte differentiation markers. The tubulointerstitial compartment and isolated tubules of Tg26-SA/+ mice also had increased Stat3 phosphorylation and expression of Stat3 target genes. We confirmed that the expression of the HIV-1 transgene and reduction of Stat3 activity did not affect T and B cell development. In conclusion, Stat3 plays a critical role in the pathogenesis of HIVAN.

Full Text

Duke Authors

Cited Authors

  • Feng, X; Lu, T-C; Chuang, PY; Fang, W; Ratnam, K; Xiong, H; Ouyang, X; Shen, Y; Levy, DE; Hyink, D; Klotman, M; D'Agati, V; Iyengar, R; Klotman, PE; He, JC

Published Date

  • October 2009

Published In

Volume / Issue

  • 20 / 10

Start / End Page

  • 2138 - 2146

PubMed ID

  • 19608706

Pubmed Central ID

  • 19608706

Electronic International Standard Serial Number (EISSN)

  • 1533-3450

Digital Object Identifier (DOI)

  • 10.1681/ASN.2008080879

Language

  • eng

Conference Location

  • United States