Abstract |
With the widespread use of combination antiretroviral agents, the incidence of HIV-associated nephropathy has decreased. Currently, HIV-infected patients live much longer and often suffer from comorbidities such as diabetes mellitus. Recent epidemiological studies suggest that concurrent HIV infection and diabetes mellitus may have a synergistic effect on the incidence of chronic kidney disease. To address this, we determined whether HIV-1 transgene expression accelerates diabetic kidney injury using a diabetic HIV-1 transgenic (Tg26) murine model. Diabetes was initially induced with low-dose streptozotocin in both Tg26 and wild-type mice on a C57BL/6 background, which is resistant to classic HIV-associated nephropathy. Although diabetic nephropathy is minimally observed on the C57BL/6 background, diabetic Tg26 mice exhibited a significant increase in glomerular injury compared with nondiabetic Tg26 mice and diabetic wild-type mice. Validation of microarray gene expression analysis from isolated glomeruli showed a significant upregulation of proinflammatory pathways in diabetic Tg26 mice. Thus, our study found that expression of HIV-1 genes aggravates diabetic kidney disease.
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Authors | Sandeep K Mallipattu, Ruijie Liu, Yifei Zhong, Ed Y Chen, Vivette D'Agati, Lewis Kaufman, Avi Ma'ayan, Paul E Klotman, Peter Y Chuang, John C He |
Journal | Kidney international
(Kidney Int)
Vol. 83
Issue 4
Pg. 626-34
(Apr 2013)
ISSN: 1523-1755 [Electronic] United States |
PMID | 23325078
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers
- Collagen Type IV
- Fusion Proteins, gag-pol
- Inflammation Mediators
- Smad3 Protein
- Smad3 protein, mouse
- Creatinine
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Topics |
- Albuminuria
(etiology, genetics, virology)
- Animals
- Biomarkers
(urine)
- Collagen Type IV
(metabolism)
- Creatinine
(urine)
- Diabetes Mellitus, Experimental
(blood, complications, immunology)
- Diabetic Nephropathies
(etiology, genetics, immunology, pathology, urine, virology)
- Disease Progression
- Fibrosis
- Fusion Proteins, gag-pol
(genetics)
- Gene Expression Profiling
(methods)
- HIV Infections
(blood, complications, genetics, immunology, virology)
- HIV-1
(genetics, immunology)
- Inflammation Mediators
(blood)
- Kidney
(immunology, metabolism, pathology, virology)
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- Oligonucleotide Array Sequence Analysis
- Phosphorylation
- Real-Time Polymerase Chain Reaction
- Reproducibility of Results
- Smad3 Protein
(metabolism)
- Time Factors
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