Volume 12, Issue 6 pp. 565-571

Signal transducer and activator of transcription 3 involvement in the development of renal interstitial fibrosis after unilateral ureteral obstruction

MASATOSHI KURATSUNE

MASATOSHI KURATSUNE

Department of Molecular and Internal Medicine, and

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TAKAO MASAKI

Corresponding Author

TAKAO MASAKI

Department of Advanced Nephrology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima City, Japan

Dr Takao Masaki, Department of Advanced Nephrology, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City 734-8551, Japan. Email: [email protected]Search for more papers by this author
TAKAYUKI HIRAI

TAKAYUKI HIRAI

Department of Molecular and Internal Medicine, and

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KEI KIRIBAYASHI

KEI KIRIBAYASHI

Department of Molecular and Internal Medicine, and

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YUKIO YOKOYAMA

YUKIO YOKOYAMA

Department of Molecular and Internal Medicine, and

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TETSUJI ARAKAWA

TETSUJI ARAKAWA

Department of Molecular and Internal Medicine, and

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NORIAKI YORIOKA

NORIAKI YORIOKA

Department of Advanced Nephrology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima City, Japan

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NOBUOKI KOHNO

NOBUOKI KOHNO

Department of Molecular and Internal Medicine, and

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First published: 09 November 2007
Citations: 73

SUMMARY:

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 α-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.

Conclusion:  STAT3 was activated in rat tubular epithelial cells and myofibroblasts after UUO, suggesting that STAT3 may contribute to the progression of interstitial fibrosis.

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