title: Expression of HIV transgene aggravates kidney injury in diabetic mice.
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.
authors: Division of Nephrology, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
authors: Sandeep K
authors: SK
authors: Mallipattu
authors: Ruijie
authors: R
authors: Liu
authors: Yifei
authors: Y
authors: Zhong
authors: Ed Y
authors: EY
authors: Chen
authors: Vivette
authors: V
authors: D'Agati
authors: Lewis
authors: L
authors: Kaufman
authors: Avi
authors: A
authors: Ma'ayan
authors: Paul E
authors: PE
authors: Klotman
authors: Peter Y
authors: PY
authors: Chuang
authors: John C
authors: JC
authors: He
mesh_terms: D000419:Albuminuria / Q000209:etiology / Q000235:genetics / Q000821:virology; D000818:Animals; D015415:Biomarkers / Q000652:urine; D024141:Collagen Type IV / Q000378:metabolism; D003404:Creatinine / Q000652:urine; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications* / Q000276:immunology; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000652:urine / Q000821:virology; D018450:Disease Progression; D005355:Fibrosis; D015685:Fusion Proteins, gag-pol / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D015658:HIV Infections / Q000097:blood / Q000150:complications* / Q000235:genetics / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D018836:Inflammation Mediators / Q000097:blood; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D051900:Smad3 Protein / Q000378:metabolism; D013997:Time Factors
chemical_list: D015415:Biomarkers; D024141:Collagen Type IV; D015685:Fusion Proteins, gag-pol; D018836:Inflammation Mediators; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D003404:Creatinine