2011 Fiscal Year Final Research Report
Uroplakin III-delta 4 as a new molecular marker for interstitial cystitis
| Project/Area Number |
21592074
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Kagawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
TYOU Ka 香川大学, 医学部, 助教 (30524061)
WU Xiu-xian 香川大学, 医学部, 助教 (10346645)
INUI Masashi 香川大学, 医学部附属病院, 講師 (40314918)
SUGIMOTO Mikio 香川大学, 医学部附属病院, 准教授 (10243768)
HONMA Yukio 東京大学, 医学部, 教授 (40165626)
YOSHIKI Tatsuhiro 京都薬科大学, 薬学部, 教授 (80230704)
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| Project Period (FY) |
2009 – 2011
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| Keywords | 間質性膀胱炎 / ウロプラキン / 非潰瘍型 / ウロプラキンデルタ4 / 分子診断 |
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| Research Abstract |
Interstitial cystitis(IC) is a chronic bladder disorder affecting approximately one million people in the United States, of whom some 90% are women. IC is characterized by urinary frequency, urinary urgency, bladder discomfort or bladder pain in the absence of any identifiable cause, such as bacterial infection. Due to lacking in a reliably objective diagnostic test, IC remains a diagnosis based on symptoms and exclusion criteria.
The apical surface of mammalian urothelium is covered by numerous rigid-appearing plaques that contribute to the permeability barrier. Uroplakins(UPs) Ia, Ib, II, and III consist of these plaques by forming heterodimer pairs(UPIa/ UPII and UPIb/ UPIII). UPIII-delta 4(UP3d4) is a splicing variant of UPIII that can be distinguished from UPIII by lacking exon 4. The whole cDNA fragment for human UP3d4 was molecularly cloned by us from a cDNA library constructed from bladder mucosa samples of a patient with vesicoureteral reflux. We investigated gene expression pr
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ofile of UPs including UP3d4 in bladder mucosa of patients with IC. One of the major findings of the study was that UP3d4 gene was significantly up-regulated in IC samples. What was more striking was that up-regulation of UP3d4 was specifically observed in non-ulcerative type IC bladder samples.
The next step of this study project is to investigate protein expression of UP3d4 in bladder urothelial cells of IC patients. For this purpose, we have raised murine monoclonal antibodies against purified UP3d4 protein which was produced by the recombinant DNA technique. Protein expression of UP3d4 was evaluable in 46 IC patients while 27 were not due to epithelial exfoliation. UP3d4 was immunohistochemically positive in 29 of 46 samples(63%). The positive rate was 80%(20/ 25) in non-ulcer type and 43%(9/ 21) in ulcer type IC(p=0. 014). UP3d4 was not detected in any of non-IC bladder mucosa. Patients with positive UP3d4 staining was younger than those with negative staining(mean age : 51. 5 vs 62. 0, p=0. 029). UP3d4 mRNA expression was identified in urine sediment cells from 24%(8/ 33) IC patients ; 18%(3/ 17) in non-ulcer type and 31%(5/ 16) ulcer type.
In conclusion, a high UP3d4 protein expression was demonstrated in urothelium of IC, especially non-ulcer type IC. Detection of UP3d4 mRNA was feasible for urine sediment cells. Further exploration is warranted to investigate the potential role of UP3d4 in pathogenesis and diagnosis of IC. Less
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Research Products
(5 results)
