Isarangkul Duangnate, Wiyakrutta Suthep, Kengkoom Kanchana, Reamtong Onrapak, Ampawong Sumate
Department of Microbiology, Faculty of Science, Mahidol University 272, Rama VI Road, Ratchathewi, Bangkok 10400, Thailand.
Office of Academic Services, National Laboratory Animal Center, Mahidol University 999, Phutthamonthon 4 Road, Salaya, Phutthamonthon, Nakhon Pathom 73170, Thailand.
Int J Clin Exp Med. 2015 Jun 15;8(6):9192-204. eCollection 2015.
The pathogenesis of congenital hydronephrosis in laboratory animals has been studied for many years, yet little is known about the underlying mechanism of this disease. In this study, we investigated a MS-based comparative proteomics approach to characterize the differently expressed proteins between kidney tissue samples of ICR/Mlac-hydro and wild-type mice. Interestingly, proteomic results exhibited several mitochondrial protein alterations especially the up-regulation of 60 kDa heat shock protein (Hsp60), stress-70 protein (GRP75) dysfunction, and down-regulation of voltage-dependent anion-selective channel protein 1 (VDAC-1). The results demonstrated that mitochondrial alteration may lead to inadequate energy-supply to maintain normal water reabsorption from the renal tubule, causing hydronephrosis. Moreover, the alteration of cytoskeleton proteins in the renal tubule, in particular the up-regulation of tubulin beta-4B chain (Tb4B) and N-myc downstream-regulated gene 1 protein (Ndr-1) may also be related due to their fundamental roles in maintaining cell morphology and tissue stability. In addition, cytoskeletal alterations may consequence to the reduction of glyceraldehydes-3-phosphate dehydrogenase (GAPDH), cytoplasmic enzyme, which modulates the capacity of structural proteins. Our findings highlight a number of target proteins that may play a crucial role in congenital hydronephrosis and emphasize that the disorder of mitochondria and cytoskeleton proteins may be involved.
先天性肾积水在实验动物中的发病机制已研究多年，但对该疾病的潜在机制仍知之甚少。在本研究中，我们采用基于质谱的比较蛋白质组学方法，对ICR/Mlac-hydro小鼠和野生型小鼠肾脏组织样本中差异表达的蛋白质进行表征。有趣的是，蛋白质组学结果显示了几种线粒体蛋白的改变，特别是60 kDa热休克蛋白（Hsp60）上调、应激70蛋白（GRP75）功能障碍以及电压依赖性阴离子选择性通道蛋白1（VDAC-1）下调。结果表明，线粒体改变可能导致能量供应不足，无法维持肾小管正常的水重吸收，从而引起肾积水。此外，肾小管中细胞骨架蛋白的改变，特别是微管蛋白β-4B链（Tb4B）和N-myc下游调控基因1蛋白（Ndr-1）的上调，也可能与之相关，因为它们在维持细胞形态和组织稳定性方面起着重要作用。此外，细胞骨架改变可能导致甘油醛-3-磷酸脱氢酶（GAPDH）减少，GAPDH是一种调节结构蛋白能力的细胞质酶。我们的研究结果突出了一些可能在先天性肾积水中起关键作用的靶蛋白，并强调线粒体和细胞骨架蛋白的紊乱可能与之有关。
