Basic Research - Neurourology & LUTS/BPH & Others(구연) (E-030)

과민성방광의 요로상피에서 분비되는 잠재적인 생체표지자 확인을 위한 단백체 분석
충남대학교 의과대학 비뇨의학교실
나현석, 이충렬, 이지용, 양승우, 이재근, 김용, 박종목, 나용길, 송기학, 임재성, 신주현
Introduction:
The urothelium directly contacts with urine, secreted proteins from the urothelium could be released into urine. In previously study, we demonstrated that urothelial protein expression is dynamically altered by OAB. These altered proteins in OAB urothelium could be used as potential diagnostic markers.
Objective: We tried to compare the profile of proteins secreted by OAB urothelium with those secreted by normal bladder urothelium to identify molecular diagnostic markers for OAB.
Methods: The study was conducted using male Sprague-Dawley rats, subdivided into sham control (n=40) and partial BOO groups (n=60). Partial BOO was induced for 2 weeks and DO was confirmed with measuring cystometry. The urothelium was carefully removed from the smooth muscle layer under a dissecting microscope and its protein expression was analyzed by LTQ-Velos mass spectrometer. The identified proteins were analyzed to discover upstream molecules, and potential biomarkers that are associated with OAB by using Ingenuity Pathway Analysis (IPA) tool.
Results: This analysis identified 17 putative upstream regulators. Complement component 3b/4b receptor 1-like, huntingtin, and inhibin α act as upstream regulators of Cryab, Aldoa, Tpm2, Myl9, Cnn1, Myh1, and C3, and may cause activation of muscle contraction. Six of the upstream regulators, huntingtin, inhibin α, integrin α2, complement component 3b/4b receptor 1-like, HNF1 homeobox B, and platelet derived growth factor family, may also affect positively the cell movement of leukocytes and neutrophils as well as cellular infiltration by leukocytes through the regulation of many other proteins identified in the urothelium. These regulators are involved primarily in inflammation and cytoskeletal organization. We identified 37 extracellular proteins that were exclusively expressed incontrol or OAB rat urothelium (Table 1).
Conclusion: These potential markers are closely related to the pathophysiological changes that occur in OAB. Detecting these proteins or their peptide fragments in urine may be a useful tool for the diagnosis. Verification of these proteins in the urine of OAB patients may be useful noninvasive diagnostic markers for OAB.
keywords : OAB, urothelial protein, noninvasive diagnostic marker

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