Uroplakin III-delta 4 as a new molecular marker for interstitial cystitis

间质性膀胱炎（IC）是一种慢性膀胱疾病，在美国约有100万人患病，其中约90%为女性。IC的特征在于在没有任何可识别的原因（例如细菌感染）的情况下的尿频、尿急、膀胱不适或膀胱疼痛。由于缺乏一个可靠的客观诊断测试，IC仍然是一个诊断的基础上的症状和排除标准。哺乳动物尿路上皮的顶端表面覆盖着许多刚性出现斑块，有助于渗透屏障。尿斑蛋白（UPs）Ia、Ib、II和III通过形成异二聚体对（UPIa/ UPII和UPIb/ UPIII）组成这些斑块。UPIII-δ 4（UP3 d4）是UPIII的剪接变体，其可以通过缺少外显子4而与UPIII区分开。我们从膀胱输尿管反流患者膀胱粘膜样品构建的cDNA文库中分子克隆了人UP3 d4的完整cDNA片段。我们研究了基因表达过程中， ...更多信息 IC患者膀胱粘膜中有大量的UPs，包括UP3 d4。本研究的主要发现之一是IC样本中UP3 d4基因显著上调。本研究的下一步工作是研究UC患者膀胱尿路上皮细胞中UP3 d4蛋白的表达。为此，我们提出了鼠单克隆抗体对纯化的UP3 d4蛋白，这是由重组DNA技术产生的。UP3 d4蛋白表达在46例IC患者中可评估，而27例由于上皮脱落而不可评估。46例标本中29例（63%）UP3 d4表达阳性。非溃疡型阳性率为80%（20/ 25），溃疡型阳性率为43%（9/ 21）（p=0. 001）。014）。UP3 d4在所有非IC膀胱粘膜中均未检测到。UP3 d4阳性患者比阴性患者更年轻（平均年龄：51岁）。五比六十二。0，p=0。029）。尿沉渣细胞中UP3 d4 mRNA表达阳性率为24%（8/ 33），非溃疡型为18%（3/ 17），溃疡型为31%（5/ 16）。尿沉渣细胞UP3 d4 mRNA的检测是可行的。UP3 d4在IC发病机制和诊断中的潜在作用有待进一步研究。少

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 … More 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