Podocyte-specific deletion of signal transducer and activator of transcription 3 attenuates nephrotoxic serum-induced glomerulonephritis

Yan Dai, Leyi Gu, Weijie Yuan, Qing Yu, Zhaohui Ni, Michael J. Ross, Lewis Kaufman, Huabao Xiong, David J. Salant, John C. He, Peter Y. Chuang

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Activation of signal transducer and activator of transcription (STAT)3 correlates with proliferation of extracapillary glomerular epithelial cells and the extent of renal injury in glomerulonephritis. To delineate the role of STAT3 in glomerular epithelial cell proliferation, we examined the development of nephrotoxic serum-induced glomerulonephritis in mice with and without podocyte-restricted STAT3 deletion. Mice with STAT3 deletion in podocytes developed less crescents and loss of renal function compared with those without STAT3 deletion. Proliferation of glomerular cells, loss of podocyte markers, and recruitment of parietal epithelial cells were found in nephritic mice without STAT3 deletion, but mitigated in nephritic mice with podocyte STAT3 deletion. Glomerular expression of pro-inflammatory STAT3 target genes was significantly reduced in nephritic mice with, compared with those without, podocyte STAT3 deletion. However, the extent of glomerular immune complex deposition was not different. Podocytes with STAT3 deletion were resistant to interleukin-6-induced STAT3 phosphorylation and pro-inflammatory STAT3 target gene expression. Thus, podocyte STAT3 activation is critical for the development of crescentic glomerulonephritis.

Original languageEnglish (US)
Pages (from-to)950-961
Number of pages12
JournalKidney international
Volume84
Issue number5
DOIs
StatePublished - Nov 2013
Externally publishedYes

Keywords

  • glomerulonephritis
  • glomerulus
  • podocyte
  • proliferation
  • signaling

ASJC Scopus subject areas

  • Nephrology

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  • Cite this

    Dai, Y., Gu, L., Yuan, W., Yu, Q., Ni, Z., Ross, M. J., Kaufman, L., Xiong, H., Salant, D. J., He, J. C., & Chuang, P. Y. (2013). Podocyte-specific deletion of signal transducer and activator of transcription 3 attenuates nephrotoxic serum-induced glomerulonephritis. Kidney international, 84(5), 950-961. https://doi.org/10.1038/ki.2013.197