Document Detail


Deletion of podocyte STAT3 mitigates the entire spectrum of HIV-1-associated nephropathy.
MedLine Citation:
PMID:  23343908     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Leyi Gu; Yan Dai; Jin Xu; Sandeep Mallipattu; Lewis Kaufman; Paul E Klotman; John C He; Peter Y Chuang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  AIDS (London, England)     Volume:  27     ISSN:  1473-5571     ISO Abbreviation:  AIDS     Publication Date:  2013 Apr 
Date Detail:
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    
Other Details:
Languages:  eng     Pagination:  1091-8     Citation Subset:  IM; X    
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MeSH Terms
Descriptor/Qualifier:
AIDS-Associated Nephropathy / etiology,  genetics,  pathology*
Albuminuria
Animals
Blotting, Western
Cell Proliferation
Cells, Cultured
Disease Models, Animal
Epithelial Cells / pathology
Gene Deletion
Gene Expression Profiling
HIV Infections / complications,  genetics,  pathology*
Humans
Kidney Glomerulus / metabolism,  pathology*
Mice
Mice, Transgenic
MicroRNAs
Podocytes / metabolism*,  pathology
Real-Time Polymerase Chain Reaction
STAT3 Transcription Factor / genetics,  metabolism*
Sclerosis
Signal Transduction / genetics
Weight Loss
Grant Support
ID/Acronym/Agency:
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
Chemical
Reg. No./Substance:
0/MicroRNAs; 0/STAT3 Transcription Factor
Comments/Corrections

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