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 (Carlton). 2012 Feb;17(2):148-59. doi: 10.1111/j.1440-1797.2011.01541.x.
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.
自噬是一种细胞内降解细胞质成分的过程，可调节细胞死亡或增殖。单侧输尿管梗阻（UUO）是梗阻肾脏进行性肾纤维化的模型。UUO 后，对侧肾脏会发生代偿性细胞增殖。我们研究了自噬在 UUO 后梗阻肾脏和对侧肾脏中的作用。
为了获得 UUO 过程中自噬的证据和模式，UUO 后 3、7 和 14 天处死大鼠。为了检查自噬抑制剂 3-甲基腺嘌呤（3-MA）的疗效，大鼠每天用腹腔注射 3-MA（30mg/kg 体重/天）治疗 7 天。
UUO 后，梗阻肾脏中的自噬呈时间依赖性诱导。3-MA 抑制自噬增强了 UUO 后梗阻肾脏中肾小管细胞凋亡和肾小管间质纤维化。在对侧肾脏中，自噬在 UUO 期间也被诱导并延长。UUO 后，3-MA 抑制自噬显著增加了对侧肾脏中增殖细胞核抗原的蛋白表达。Akt-雷帕霉素靶蛋白（mTOR）信号通路参与了双侧肾脏 UUO 后自噬的诱导。
我们的研究结果表明，UUO 诱导的自噬在梗阻肾脏中具有保护作用，在对侧肾脏中通过 Akt-mTOR 信号通路对代偿性细胞增殖具有调节作用。
