|Deletion of podocyte STAT3 mitigates the entire spectrum of HIV-1-associated nephropathy.|
|PMID: 23343908 Owner: NLM Status: MEDLINE|
|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.
|Leyi Gu; Yan Dai; Jin Xu; Sandeep Mallipattu; Lewis Kaufman; Paul E Klotman; John C He; Peter Y Chuang|
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|Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.|
|Title: AIDS (London, England) Volume: 27 ISSN: 1473-5571 ISO Abbreviation: AIDS Publication Date: 2013 Apr|
|Created Date: 2013-08-01 Completed Date: 2013-11-12 Revised Date: 2014-04-25|
Medline Journal Info:
|Nlm Unique ID: 8710219 Medline TA: AIDS Country: England|
|Languages: eng Pagination: 1091-8 Citation Subset: IM; X|
|APA/MLA Format Download EndNote Download BibTex|
Disease Models, Animal
Epithelial Cells / pathology
Gene Expression Profiling
HIV Infections / complications, genetics, pathology*
Kidney Glomerulus / metabolism, pathology*
Podocytes / metabolism*, pathology
Real-Time Polymerase Chain Reaction
STAT3 Transcription Factor / genetics, metabolism*
Signal Transduction / genetics
|1R01DK078897/DK/NIDDK NIH HHS; 1R01DK088541-01A1/DK/NIDDK NIH HHS; 5K08DK082760/DK/NIDDK NIH HHS; K08 DK082760/DK/NIDDK NIH HHS; P01 DK056492/DK/NIDDK NIH HHS; P01DK056492/DK/NIDDK NIH HHS; R01 DK078897/DK/NIDDK NIH HHS; R01 DK088541/DK/NIDDK NIH HHS; RC4 DK090860/DK/NIDDK NIH HHS; RC4DK090860/DK/NIDDK NIH HHS|
|0/MicroRNAs; 0/STAT3 Transcription Factor|
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