Activation of Notch signaling pathway in HIV-associated nephropathy

Madhulika Sharma, Shannon Callen, Da Zhang, Pravin C. Singhal, Gregory B. Vanden Heuvel, Shilpa J Buch

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Objective: HIV-associated nephropathy (HIVAN) is characterized by the development of glomerulosclerosis and is associated with glomerular epithelial cell proliferation. It has recently been shown that activation of the Notch signaling pathway in podocytes results in glomerulosclerosis and podocyte proliferation. To determine whether Notch signaling is involved in renal disorder associated with HIVAN, we evaluated the expression of Notch receptors in HIVAN. DESIGN: We evaluated the expression of the Notch signaling pathway using an HIV-transgenic (HIV-Tg) rat model of HIVAN, and biopsy samples from HIVAN and normal controls. Methods: Paraffin sections and kidney lysates were used for immunohistochemistry, immunofluorescence and western blot analysis. Results: A collapsing variant of glomerulosclerosis and focal segmental sclerosis was observed in HIV-Tg rats. Glomeruli of HIV-Tg rats demonstrated activation of Notch1 and Notch4, as determined by the presence of the intracellular domains. In addition, we observed increased expression of the Notch target protein, hairy enhancer of split homolog-1 in glomeruli of these animals. The expression of the Groucho homolog transducin-like enhancer protein 4, a Notch effector protein, and the homeodomain protein cut homeobox 1 were also significantly increased in glomeruli of HIV-Tg rats, and this was associated with decreased expression of the cyclin kinase inhibitor p27. Intriguingly, renal biopsy samples from HIVAN patients also showed upregulation of cleaved Notch1 and Notch4 in the glomeruli compared with the expression in normal kidneys. Conclusion: Our results demonstrate activation of Notch signaling pathway in HIVAN, thereby underscoring its role in disease pathogenesis.

Original languageEnglish (US)
Pages (from-to)2161-2170
Number of pages10
JournalAIDS
Volume24
Issue number14
DOIs
StatePublished - Sep 10 2010

Fingerprint

AIDS-Associated Nephropathy
Transgenic Rats
Notch Receptors
HIV
Kidney
Podocytes
Transducin
Homeodomain Proteins
Biopsy
Focal Segmental Glomerulosclerosis
Cyclins
Homeobox Genes
Sclerosis
Paraffin
Fluorescent Antibody Technique
Phosphotransferases
Up-Regulation
Western Blotting
Epithelial Cells
Immunohistochemistry

Keywords

  • HIV-associated nephropathy
  • Notch
  • cut homeobox 1
  • glomerulosclerosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Sharma, M., Callen, S., Zhang, D., Singhal, P. C., Vanden Heuvel, G. B., & Buch, S. J. (2010). Activation of Notch signaling pathway in HIV-associated nephropathy. AIDS, 24(14), 2161-2170. https://doi.org/10.1097/QAD.0b013e32833dbc31

Activation of Notch signaling pathway in HIV-associated nephropathy. / Sharma, Madhulika; Callen, Shannon; Zhang, Da; Singhal, Pravin C.; Vanden Heuvel, Gregory B.; Buch, Shilpa J.

In: AIDS, Vol. 24, No. 14, 10.09.2010, p. 2161-2170.

Research output: Contribution to journalArticle

Sharma, M, Callen, S, Zhang, D, Singhal, PC, Vanden Heuvel, GB & Buch, SJ 2010, 'Activation of Notch signaling pathway in HIV-associated nephropathy', AIDS, vol. 24, no. 14, pp. 2161-2170. https://doi.org/10.1097/QAD.0b013e32833dbc31
Sharma M, Callen S, Zhang D, Singhal PC, Vanden Heuvel GB, Buch SJ. Activation of Notch signaling pathway in HIV-associated nephropathy. AIDS. 2010 Sep 10;24(14):2161-2170. https://doi.org/10.1097/QAD.0b013e32833dbc31
Sharma, Madhulika ; Callen, Shannon ; Zhang, Da ; Singhal, Pravin C. ; Vanden Heuvel, Gregory B. ; Buch, Shilpa J. / Activation of Notch signaling pathway in HIV-associated nephropathy. In: AIDS. 2010 ; Vol. 24, No. 14. pp. 2161-2170.
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