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Skip Navigation LinksHome > April 24, 2013 - Volume 27 - Issue 7 > Deletion of podocyte STAT3 mitigates the entire spectrum of...
AIDS:
doi: 10.1097/QAD.0b013e32835f1ea1
Basic Science: Concise Communication

Deletion of podocyte STAT3 mitigates the entire spectrum of HIV-1-associated nephropathy

Gu, Leyia,b,*; Dai, Yana,c,*; Xu, Jina; Mallipattu, Sandeepa; Kaufman, Lewisa; Klotman, Paul E.d; He, John C.a,e; Chuang, Peter Y.a

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Abstract

Objective: HIV-1 gene expression in kidney epithelial cells is thought to be responsible for the pathogenesis of HIV-1-associated nephropathy (HIVAN). Signal transducer and activator of transcription (STAT) 3 signaling is activated in podocytes of patients with HIVAN and drives the dedifferentiation and proliferation of podocytes in culture. We confirm here that deletion of podocyte STAT3 is sufficient to mitigate the glomerular as well as tubulointerstitial findings of HIVAN.

Methods: To demonstrate the functional role of podocyte STAT3 in the pathogenesis of HIVAN we compared the development of HIVAN in Tg26 HIV-transgenic mice with and without deletion of STAT3 in the podocyte.

Results: Tg26 mice with podocyte-specific STAT3 deletion developed significantly less weight loss, albuminuria, and renal function impairment compared to Tg26 mice without STAT3 deletion. Tg26 mice with podocyte STAT3 deletion also had significantly less glomerular collapse, sclerosis, epithelial cell hyperplasia, podocyte dedifferentiation, and proinflammatory STAT3 target gene expression; and tubulointerstitial changes of HIVAN, including tubular atrophy, degeneration, apoptosis, and lymphocyte infiltration, were also significantly reduced compared to Tg26 mice without STAT3 deletion.

Conclusion: Development of glomerular as well as tubulointerstitial injuries in the Tg26 HIVAN model is dependent on podocyte STAT3 expression. Inhibition of STAT3 could be a potential adjunctive therapy for the treatment of HIVAN.

© 2013 Lippincott Williams & Wilkins, Inc.

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