Activation of signal transducer and activator of transcription 3 correlates with cell proliferation and renal injury in human glomerulonephritis.
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.
Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima City 734-8551, Japan.
Tetsuji
T
Arakawa
Takao
T
Masaki
Takayuki
T
Hirai
Shigehiro
S
Doi
Masatoshi
M
Kuratsune
Koji
K
Arihiro
Nobuoki
N
Kohno
Noriaki
N
Yorioka
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D016022:Case-Control Studies; D049109:Cell Proliferation; D005260:Female; D005921:Glomerulonephritis / Q000378:metabolism* / Q000473:pathology; D005922:Glomerulonephritis, IGA / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology*; D008181:Lupus Nephritis / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014657:Vasculitis / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human