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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Albuminuria / etiology
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Albuminuria / genetics
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Albuminuria / virology
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Animals
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Biomarkers / urine
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Collagen Type IV / metabolism
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Creatinine / urine
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Diabetes Mellitus, Experimental / blood
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Diabetes Mellitus, Experimental / complications*
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Diabetes Mellitus, Experimental / immunology
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Diabetic Nephropathies / etiology*
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Diabetic Nephropathies / genetics
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Diabetic Nephropathies / immunology
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Diabetic Nephropathies / pathology
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Diabetic Nephropathies / urine
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Diabetic Nephropathies / virology
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Disease Progression
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Fibrosis
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Fusion Proteins, gag-pol / genetics
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Gene Expression Profiling / methods
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HIV Infections / blood
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HIV Infections / complications*
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HIV Infections / genetics
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HIV Infections / immunology
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HIV Infections / virology
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HIV-1 / genetics*
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HIV-1 / immunology
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Inflammation Mediators / blood
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Kidney / immunology
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Kidney / metabolism
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Kidney / pathology
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Kidney / virology*
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Oligonucleotide Array Sequence Analysis
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Phosphorylation
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Real-Time Polymerase Chain Reaction
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Reproducibility of Results
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Smad3 Protein / metabolism
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Time Factors
Substances
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Biomarkers
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Collagen Type IV
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Fusion Proteins, gag-pol
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Inflammation Mediators
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Smad3 Protein
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Smad3 protein, mouse
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Creatinine