Área Farmacología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, CONICET, Argentina.
Área Farmacología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, CONICET, Argentina.
Toxicol Lett. 2019 Oct 1;313:169-177. doi: 10.1016/j.toxlet.2019.07.010. Epub 2019 Jul 5.
Acute kidney injury (AKI) is a heterogeneous clinical syndrome with diverse outcomes. The recovery from AKI has prognostic importance. Little research has been done in order to find biomarkers that can predict recovery from AKI. Cav-2 is one of the main constituents of caveolae and is expressed in kidney. This study analyzed the time course of Cav-2 urinary excretion and renal expression in rats treated with cisplatin. Male Wistar rats were injected with cisplatin (5 mg/kg b.w., i.p.), and the studies were performed after 2, 4 and 14 days. Cav-2 abundance was evaluated in urine, in renal homogenates and in apical membranes by Western blotting. Cav-2 in urine was increased only 14 days after treatment, in the recovery phase of cisplatin-induced AKI. These results show that Cav-2 in urine could be useful as a biomarker of renal recovery, but not as an early biomarker of cisplatin-induced AKI. Cav-2 expression in total renal homogenates was not modified with treatment, but a down-regulation of Cav-2 in apical membranes was observed in treated animals. We hypothesize that Cav-2 internalizes into renal cells from their apical membrane in response to cisplatin, and regulates in this manner different signaling proteins involved in the physiopathology of renal damage.
急性肾损伤(AKI)是一种具有不同结局的异质性临床综合征。AKI 的恢复具有预后意义。为了寻找能够预测 AKI 恢复的生物标志物,已经进行了一些研究。Cav-2 是小窝的主要组成部分之一,在肾脏中表达。本研究分析了顺铂处理大鼠的 Cav-2 尿排泄和肾表达的时间过程。雄性 Wistar 大鼠腹腔注射顺铂(5mg/kg b.w.),在 2、4 和 14 天后进行研究。通过 Western blot 分析 Cav-2 在尿液、肾匀浆和顶端膜中的丰度。只有在顺铂诱导的 AKI 恢复期的 14 天后,尿液中的 Cav-2 才增加。这些结果表明,尿液中的 Cav-2 可能是肾恢复的有用生物标志物,但不是顺铂诱导的 AKI 的早期生物标志物。Cav-2 在总肾匀浆中的表达未随治疗而改变,但在处理动物中观察到顶端膜中 Cav-2 的下调。我们假设 Cav-2 从顺铂的顶端膜内化到肾细胞中,并以这种方式调节参与肾损伤病理生理学的不同信号蛋白。