title: Mitochondrial and cytoskeletal alterations are involved in the pathogenesis of hydronephrosis in ICR/Mlac-hydro mice.
abstract: 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.
authors: Department of Microbiology, Faculty of Science, Mahidol University 272, Rama VI Road, Ratchathewi, Bangkok 10400, Thailand.
authors: Duangnate
authors: D
authors: Isarangkul
authors: Department of Microbiology, Faculty of Science, Mahidol University 272, Rama VI Road, Ratchathewi, Bangkok 10400, Thailand.
authors: Suthep
authors: S
authors: Wiyakrutta
authors: Office of Academic Services, National Laboratory Animal Center, Mahidol University 999, Phutthamonthon 4 Road, Salaya, Phutthamonthon, Nakhon Pathom 73170, Thailand.
authors: Kanchana
authors: K
authors: Kengkoom
authors: Department of Molecular Tropical Medicine and Genetic, Faculty of Tropical Medicine, Mahidol University 420/6, Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand.
authors: Onrapak
authors: O
authors: Reamtong
authors: Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University 420/6, Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand.
authors: Sumate
authors: S
authors: Ampawong
keywords: Cytoskeleton; ICR/Mlac-hydro mice; hydronephrosis; mitochondria; pathogenesis; proteomic