Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
Mol Cell Endocrinol. 2013 Dec 5;381(1-2):168-74. doi: 10.1016/j.mce.2013.07.028. Epub 2013 Aug 6.
Urotensin II (UII) is a cyclic vasoactive peptide which is mainly expressed in kidneys. Although elevated plasma UII levels are associated with renal impairment, the influence of UII on renal injury is unclear. In this study, we monitored the influence of UII on gentamicin-induced apoptosis in rat tubular cells (NRK-52E). We found that UII significantly reduced gentamicin-induced apoptosis and apoptotic signals. Blocking endogenous UII secretion caused cells to be more susceptible to gentamicin. In gentamicin-treated mice, UII also expressed protective effect on renal tubular cells. UII was also found to induce prostacyclin (PGI2) production, which caused peroxisomal proliferator-activated receptor α (PPARα) activation as revealed by both PGI2 synthase siRNA transfection and piroxicam treatment. Blockage of PPARα by siRNA transfection inhibited UII-induced Akt phosphorylation and the antiapoptotic effect of UII. Our results suggest that UII can protect renal tubular cells from gentamicin-induced apoptosis through PGI2-mediated PPARα and Akt activation.
尾加压素 II（UII）是一种主要在肾脏中表达的环状血管活性肽。尽管血浆 UII 水平升高与肾功能损害有关，但 UII 对肾脏损伤的影响尚不清楚。在这项研究中，我们监测了 UII 对庆大霉素诱导的大鼠肾小管细胞（NRK-52E）凋亡的影响。我们发现 UII 可显著减少庆大霉素诱导的细胞凋亡和凋亡信号。阻断内源性 UII 分泌会使细胞对庆大霉素更敏感。在庆大霉素处理的小鼠中，UII 对肾小管细胞也表现出保护作用。还发现 UII 可诱导前列环素（PGI2）的产生，PGI2 合酶 siRNA 转染和吡罗昔康处理均显示 UII 诱导过氧化物酶体增殖物激活受体α（PPARα）的激活。用 siRNA 转染阻断 PPARα 抑制了 UII 诱导的 Akt 磷酸化和 UII 的抗凋亡作用。我们的结果表明，UII 可通过 PGI2 介导的 PPARα 和 Akt 激活来保护肾小管细胞免受庆大霉素诱导的凋亡。
