Journal Article

Activation of signal transducer and activator of transcription 3 correlates with cell proliferation and renal injury in human glomerulonephritis

Tetsuji Arakawa, Takao Masaki, Takayuki Hirai, Shigehiro Doi, Masatoshi Kuratsune, Koji Arihiro, Nobuoki Kohno and Noriaki Yorioka

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 23, issue 11, pages 3418-3426
Published in print November 2008 | ISSN: 0931-0509
Published online June 2008 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfn314
Activation of signal transducer and activator of transcription 3 correlates with cell proliferation and renal injury in human glomerulonephritis

Show Summary Details

Preview

Background. Signal transducer and activator of transcription (STAT) 3 plays an important role in the regulation of cell proliferation. However, the mechanism of STAT3 activation in human glomerulonephritis is unclear.

Methods. STAT3 activation was determined using immunohistochemistry for phosphorylated STAT3 (p-STAT3) in normal human kidney and various types of glomerulonephritis. We also identified the cell exhibiting activated p-STAT3 expression in human glomerulonephritis and correlated STAT3 activation with renal function and histologic injury.

Results. p-STAT3 staining was identified in glomeruli and some tubules in normal human kidney. p-STAT3 positive glomerular cells were significantly increased in lupus nephritis, IgA nephropathy and vasculitis compared with normal kidney. p-STAT3 positive tubulointerstitial cells were significantly increased in IgA nephropathy and vasculitis compared with normal kidney. Glomerular and tubulointerstitial p-STAT3 staining was significantly decreased after steroid therapy. There was a significant correlation between the number of p-STAT3 positive cells and the number of PCNA positive glomerular and tubulointerstitial cells in all cases of glomerulonephritis. Furthermore, renal function inversely correlated with the number of p-STAT3 positive glomerular and tubulointerstitial cells in all cases of glomerulonephritis.

Conclusions. The present study has identified STAT3 activation in normal human kidney and a marked increase in STAT3 activation in many forms of glomerulonephritis. The correlation of STAT3 activation with clinical and histologic parameters suggests that this pathway plays an important role in the pathogenesis of kidney disease. Furthermore, localization of STAT3 activation to individual cell types suggests that this pathway may play a pivotal role in promoting renal inflammation and fibrosis.

Keywords: cell proliferation; glomerulonephritis; renal injury; STAT3

Journal Article.  4810 words.  Illustrated.

Subjects: Nephrology

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.