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Proteomic analyses of molecular factors associated with obstructive megaureter dysfunction

Authors
 Hyo Jin Kang  ;  Ji Hee Jun  ;  Sang Won Han 
Citation
 INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE, Vol.12(9) : 11938-11945, 2019 
Journal Title
 INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE 
Issue Date
2019
Keywords
Obstructive megaureter ; smooth muscle cell ; tropomyosin 1 (TPM1) ; 2D electrophoresis ; proteomics
Abstract
Objective: The underlying pathophysiology of obstructive and refluxing megaureters is poorly understood. The current study investigated the molecular mechanisms of ureter dysfunction, identifying proteins via proteomic analyses. Materials and methods: Megaureter and normal ureter tissues were used to examine differentially-expressed proteins. Smooth muscle cells (SMCs) of obstructive megaureters were obtained from five patients that underwent open ureteroneocystostomy surgeries and five control patients with low-grade vesicoureteral reflux. SMCs were cultured in M199 medium supplemented with 10% fetal bovine serum and 1% antibiotics. Aiming to identify differentially-expressed proteins, protein spots separated by 2D gel electrophoresis were matched. They were then analyzed using PDQuest software and nanoflow LC-ESI-MS-MS. Results: In the current study, α-tropomyosin, a protein associated with the contraction and migration of SMCs, was selected from several analyzed proteins, investigating its relationship with megaureters. When TPM1 was artificially overexpressed in normal ureter SMCs, a significant change in morphology was observed. In addition, the rate of apoptosis was increased in transfected SMCs, compared to that in control SMCs. Conclusion: Abnormal overexpression of TPM1 in ureter SMCs may induce defects in contractility and increase apoptosis rates. Empty spaces caused by apoptosis may then be preferentially filled with connective tissues, rather than slowly migrating SMCs. As a result, contractility is reduced, leading to the development of a dilated ureter.
Files in This Item:
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Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Urology (비뇨의학교실) > 1. Journal Papers
Yonsei Authors
Han, Sang Won(한상원) ORCID logo https://orcid.org/0000-0003-0941-1300
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/173053
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