Article

The role of autophagy in unilateral ureteral obstruction rat model

Department of Anatomy and MRC for Cell Death Disease Research Center, Bucheon Saint Mary’s Hospital, Sosa-dong, Wonmi-gu, Bucheon-si, Geoynggi-do, 420-717 Korea.
Nephrology (Impact Factor: 1.86). 11/2011; 17(2):148-59. DOI: 10.1111/j.1440-1797.2011.01541.x
Source: PubMed

ABSTRACT Autophagy is a cellular process of degradation of damaged cytoplasmic components and regulates cell death or proliferation. Unilateral ureteral obstruction (UUO) is a model of progressive renal fibrosis in the obstructed kidney. And UUO is followed by compensatory cellular proliferation in the contralateral kidney. We investigate the role of autophagy in the obstructed kidney and contralateral kidney after UUO.
To obtain the evidence and the patterns of autophagy during UUO, the rats were sacrificed 3, 7 and 14 days after UUO. To examine the efficacy of the autophagy inhibitors, 3-methyladenine (3-MA), the rats were treated daily with intraperitoneal injection of 3-MA (30 mg/kg per day) for 7 days.
After UUO, autophagy was induced in the obstructed kidney in a time-dependent manner. Inhibition of autophagy by 3-MA enhanced tubular cell apoptosis and tubulointerstitial fibrosis in the obstructed kidney after UUO. In the contralateral kidney, autophagy was also induced and prolonged during UUO. Inhibition of autophagy by 3-MA increased the protein expression of proliferating cell nuclear antigen significantly in the contralateral kidney after UUO. The Akt-mammalian target of rapamycin (mTOR) signalling pathway was involved in the induction of autophagy after UUO in both kidneys.
Our present results support that autophagy induced by UUO has a renoprotective role in the obstructed kidney and regulatory role of compensatory cellular proliferation in the contralateral kidney through Akt-mTOR signalling pathway.

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