HIV-1 induces renal epithelial dedifferentiation in a transgenic model of HIV-associated nephropathy

Laura Barisoni-Thomas, Leslie A. Bruggeman, Peter Mundel, Vivette D. D'Agati, Paul E. Klotman

Research output: Contribution to journalArticle

155 Citations (Scopus)

Abstract

Background: Human immunodeficiency virus-associated nephropathy (HIVAN) is the most common cause of renal failure in HIV-1-seropositive patients. Recent studies using an HIV-1 transgenic mouse model have demonstrated that expression of HIV-1 in the kidney is required for the development of HIVAN. What has remained unclear, however, is the renal cell type responsible for pathogenesis and the essential pathological process. Methods: To address these issues, we used a transgenic murine model of HIVAN. We identified the cell types in kidney in which HIV transgene expression occurs using in situ hybridization. We evaluated evidence of proliferation by immunocytochemical analysis using an antibody to Ki-67 and cell type-specific markers, including WT-1, synaptopodin, Na+,K+-ATPase, adducin, and desmin. TUNEL assay was used to evaluate apoptosis. Results: We found that glomerular and tubular epithelial cells express the HIV-1 transgene early in the disease process when renal architecture is well preserved. Transgene expression is lost, however, in tubular epithelial cells when they lose their differentiated cuboidal phenotype. In glomerular epithelial cells, dedifferentiation occurs with reduced expression of WT-1 and synaptopodin, in association with activation of desmin expression. Tubular microcysts also form with mislocalization of Na+,K+-ATPase expression to the lateral and apical cellular membranes. Conclusions: These studies support the hypothesis that the glomerular and renal epithelial cells are the primary targets of HIV-1 pathogenesis in the kidney. The essential pathologic process is dysregulation of the epithelial cell cycle with increased proliferation, apoptosis, cellular dedifferentiation, and altered cellular polarity.

Original languageEnglish
Pages (from-to)173-181
Number of pages9
JournalKidney International
Volume58
Issue number1
DOIs
StatePublished - Jul 15 2000
Externally publishedYes

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AIDS-Associated Nephropathy
HIV-1
Kidney
Epithelial Cells
Transgenes
Desmin
Pathologic Processes
Cell Dedifferentiation
Apoptosis
In Situ Nick-End Labeling
Transgenic Mice
In Situ Hybridization
Renal Insufficiency
Cell Cycle
Cell Proliferation
HIV
Phenotype
Membranes
Antibodies

Keywords

  • AIDS
  • Chronic renal failure
  • Glomerular cells
  • Ki-67 cell type specific markers
  • Kidney and HIV
  • Podocytes
  • Virus

ASJC Scopus subject areas

  • Nephrology

Cite this

HIV-1 induces renal epithelial dedifferentiation in a transgenic model of HIV-associated nephropathy. / Barisoni-Thomas, Laura; Bruggeman, Leslie A.; Mundel, Peter; D'Agati, Vivette D.; Klotman, Paul E.

In: Kidney International, Vol. 58, No. 1, 15.07.2000, p. 173-181.

Research output: Contribution to journalArticle

Barisoni-Thomas, Laura ; Bruggeman, Leslie A. ; Mundel, Peter ; D'Agati, Vivette D. ; Klotman, Paul E. / HIV-1 induces renal epithelial dedifferentiation in a transgenic model of HIV-associated nephropathy. In: Kidney International. 2000 ; Vol. 58, No. 1. pp. 173-181.
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