Southgate Jennifer, Varley Claire L, Garthwaite Mary A E, Hinley Jennifer, Marsh Fiona, Stahlschmidt Jens, Trejdosiewicz Ludwik K, Eardley Ian
Jack Birch Unit of Molecular Carcinogenesis, Department of Biology, University of York, York, UK.
BJU Int. 2007 Jun;99(6):1506-16. doi: 10.1111/j.1464-410X.2007.06795.x.
To develop a novel in vitro approach to test the hypothesis that failure of urothelial differentiation underlies the aetiopathology of interstitial cystitis (IC), where there is evidence of compromised urinary barrier function, as benign dysfunctional bladder disease encompass several poorly understood clinically defined conditions, including IC, idiopathic detrusor overactivity (IDO) and stress urinary incontinence (SUI).
Biopsy-derived urothelial cells from dysfunctional bladder biopsies were propagated as finite cell lines and examined for their capacity to differentiate in vitro, as assessed by the acquisition of a transitional cell morphology, a switch from a cytokeratin (CK)13(lo)/CK14(hi) to a CK13(hi)/CK14(lo) phenotype, expression of claudin 3, 4 and 5 proteins, and induction of uroplakin gene transcription.
Two of 12 SUI cell lines showed early senescent changes in culture and were not characterized further; one of seven IC, one of five IDO and a further three SUI cell lines had some evidence of senescence at passage 3. Of the seven IC-derived cell lines, four showed a near normal range of differentiation-associated responses, but the remainder showed little or no response. Most IDO cell lines (four of five) showed a normal differentiation response, but at least three of the 10 SUI cell lines showed some compromise of differentiation potential.
This study supports the existence of a subset of patients with IC in whom a failure of urothelial cytodifferentiation might contribute to the disease, and provides a novel platform for investigating the cell biology of urothelium from SUI and other benign dysfunctional conditions.
提出一种新的体外方法，以验证如下假说：在间质性膀胱炎（IC）的病因病理学中，尿路上皮分化失败是其基础，IC存在尿屏障功能受损的证据，因为良性膀胱功能障碍性疾病包括几种临床定义尚不清楚的病症，如IC、特发性逼尿肌过度活动症（IDO）和压力性尿失禁（SUI）。
从功能障碍性膀胱活检组织中获取的活检来源的尿路上皮细胞作为有限细胞系进行培养，并检测其体外分化能力，评估指标包括获得移行细胞形态、从细胞角蛋白（CK）13（低）/CK14（高）表型转变为CK13（高）/CK14（低）表型、紧密连接蛋白3、4和5的表达以及uroplakin基因转录的诱导。
12个SUI细胞系中有2个在培养中显示出早期衰老变化，未作进一步鉴定；7个IC细胞系中的1个、5个IDO细胞系中的1个以及另外3个SUI细胞系在传代3时出现了一些衰老迹象。在7个IC来源的细胞系中，4个显示出与分化相关反应的接近正常范围，但其余细胞系几乎没有或没有反应。大多数IDO细胞系（5个中的4个）显示出正常的分化反应，但10个SUI细胞系中至少有3个显示出分化潜能的一些受损。
本研究支持存在一部分IC患者，其中尿路上皮细胞分化失败可能导致该疾病，并为研究SUI和其他良性功能障碍性疾病的尿路上皮细胞生物学提供了一个新平台。
