[Effects of curcumin on the epithelial mesenchymal transition and TGF-beta/Smads signaling pathway in unilateral ureteral obstruction rats].
OBJECTIVE
To observe the effects of curcumin on the epithelial mesenchymal transition (EMT) and TGF-beta/Smads signal pathway in unilateral ureteral obstruction (UUO) rats.


METHODS
UUO rat model was established. Rats were divided into the sham-operation group, the model group, the 1st curcumin group, and the 2nd curcumin group, respectively. From the 2nd day after surgery, rats of the 1st curcumin group were administrated with curcumin by gastrogavage at the daily dose of 100 mg/kg. From the 10th day after surgery, rats of the 2nd curcumin group were administrated with curcumin by gastrogavage at the daily dose of 100 mg/kg. Equal volume of normal saline was given to rats by gastrogavage in the sham-operation group and the model group. On the 28th day after surgery rats were killed. The renal tissues of the obstructed side were taken out. The distribution of mice alpha-smooth muscle actin (alpha-SMA) and E-cadherin expressions were observed using immunohistochemical method. Transforming growth factor-beta 1 (TGF-beta 1), P-Smad2, P-Smad3, and Smad7 expressions were detected by Western blot. TGF-beta 1, transforming growth factor-beta receptor I (TbetaRI), collagen-I (Col-I), and collagen-III (Col-III) mRNA expressions were detected by Real-time fluorescent quantitative PCR.


RESULTS
alpha-SMA expressions were obviously enhanced, E-cadherin expressions obviously weakened, the protein expression levels of P-Smad2 and P-Smad3, protein and mRNA expression levels of TGF-beta 1, TbetaRI mRNA, Col-I mRNA, and Col-III mRNA obviously up-regulated, Smad7 protein expressions obviously decreased (all P<0.01) in the renal tissues of rats in the UUO group. In the 1st curcumin group and the 2nd curcumin group, the protein expressions of alpha-SMA, P-Smad2, P-Smad3, and TGF-beta 1; mRNA expression levels of TGF-beta 1, TbetaRI mRNA, Col-I, and Col-III obviously decreased (P<0.05, P< 0.01), while the protein expressions of E-cadherin and Smad7 obviously increased (P<0.05, P<0.01).


CONCLUSIONS
Curcumin could intervene several sites of the TGF-beta/Smads signal transduction pathway of UUO rats, inhibit the occurrence of EMT of renal tubular epithelial cells, thus attenuating the tubulo-interstitial fibrosis.
Department of Development Plan, Beijing University of Chinese Medicine, Beijing 100029. liyubeijing1973@163.com
Yu
Y
Li
Zhao-qing
ZQ
Chen
Ya-dong
YD
Li
D000818:Animals; D003474:Curcumin / Q000494:pharmacology*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D007684:Kidney Tubules / Q000166:cytology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014517:Ureteral Obstruction / Q000378:metabolism*
D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D003474:Curcumin