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

Publication ,  Journal Article
Barisoni, L; Bruggeman, LA; Mundel, P; D'Agati, VD; Klotman, PE
Published in: Kidney Int
July 2000

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.

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Published In

Kidney Int

DOI

ISSN

0085-2538

Publication Date

July 2000

Volume

58

Issue

1

Start / End Page

173 / 181

Location

United States

Related Subject Headings

  • WT1 Proteins
  • Urology & Nephrology
  • Transgenes
  • Transcription Factors
  • Sodium-Potassium-Exchanging ATPase
  • Microfilament Proteins
  • Mice, Transgenic
  • Mice
  • Kidney Glomerulus
  • Kidney Failure, Chronic
 

Citation

APA
Chicago
ICMJE
MLA
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Barisoni, L., Bruggeman, L. A., Mundel, P., D’Agati, V. D., & Klotman, P. E. (2000). HIV-1 induces renal epithelial dedifferentiation in a transgenic model of HIV-associated nephropathy. Kidney Int, 58(1), 173–181. https://doi.org/10.1046/j.1523-1755.2000.00152.x
Barisoni, L., L. A. Bruggeman, P. Mundel, V. D. D’Agati, and P. E. Klotman. “HIV-1 induces renal epithelial dedifferentiation in a transgenic model of HIV-associated nephropathy.Kidney Int 58, no. 1 (July 2000): 173–81. https://doi.org/10.1046/j.1523-1755.2000.00152.x.
Barisoni L, Bruggeman LA, Mundel P, D’Agati VD, Klotman PE. HIV-1 induces renal epithelial dedifferentiation in a transgenic model of HIV-associated nephropathy. Kidney Int. 2000 Jul;58(1):173–81.
Barisoni, L., et al. “HIV-1 induces renal epithelial dedifferentiation in a transgenic model of HIV-associated nephropathy.Kidney Int, vol. 58, no. 1, July 2000, pp. 173–81. Pubmed, doi:10.1046/j.1523-1755.2000.00152.x.
Barisoni L, Bruggeman LA, Mundel P, D’Agati VD, Klotman PE. HIV-1 induces renal epithelial dedifferentiation in a transgenic model of HIV-associated nephropathy. Kidney Int. 2000 Jul;58(1):173–181.
Journal cover image

Published In

Kidney Int

DOI

ISSN

0085-2538

Publication Date

July 2000

Volume

58

Issue

1

Start / End Page

173 / 181

Location

United States

Related Subject Headings

  • WT1 Proteins
  • Urology & Nephrology
  • Transgenes
  • Transcription Factors
  • Sodium-Potassium-Exchanging ATPase
  • Microfilament Proteins
  • Mice, Transgenic
  • Mice
  • Kidney Glomerulus
  • Kidney Failure, Chronic