Signal transducer and activator of transcription 3 involvement in the development of renal interstitial fibrosis after unilateral ureteral obstruction.
BACKGROUND
In vitro studies suggest that the signal transducer and activator of transcription (STAT) plays a critical role in renal fibrosis. However, the process of STAT activation in vivo remains unclear. This study in rats aimed to localize STAT3 activation within the kidney and examine the in vivo relationship between STAT3 activation and renal fibrosis.


METHODS
Unilateral ureteral obstruction (UUO) was induced in the rats and the kidneys examined 3 or 7 days after obstruction. Activation of STAT3 in western blot and immunohistochemical analyses was identified by the phosphorylated form of STAT3 (pSTAT3).


RESULTS
Myofibroblasts were identified by alpha-smooth muscle actin expression and were upregulated in obstructed kidneys. pSTAT3 was localized mainly in tubular epithelial cells of collecting ducts in normal and obstructed kidneys and interstitial cells in obstructed kidneys. After UUO, western blotting showed a fourfold increase in pSTAT3, with a peak at day 7. Immunostaining showed a sixfold increase in pSTAT3 at day 7 in tubular epithelial cells and a 2500-fold increase at day 7 in interstitial cells.


CONCLUSIONS
STAT3 was activated in rat tubular epithelial cells and myofibroblasts after UUO, suggesting that STAT3 may contribute to the progression of interstitial fibrosis.
Kuratsune
Masatoshi
M
Department of Molecular and Internal Medicine, Graduate School of Medical Sciences, Hiroshima University, Hiroshima City, Japan.
Masaki
Takao
T
Hirai
Takayuki
T
Kiribayashi
Kei
K
Yokoyama
Yukio
Y
Arakawa
Tetsuji
T
Yorioka
Noriaki
N
Kohno
Nobuoki
N
D000818:Animals; D015153:Blotting, Western; D005355:Fibrosis; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000502:physiology*; D014517:Ureteral Obstruction / Q000150:complications*
D050796:STAT3 Transcription Factor