Barrier-Forming Potential of Epithelial Cells from the Exstrophic Bladder.
Barrier-Forming Potential of Epithelial Cells from the Exstrophic Bladder.
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DOI：
10.1016/j.ajpath.2022.03.009
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发表时间：
2022-06
影响因子：
6
通讯作者：
Southgate, Jennifer
中科院分区：
文献类型：
--
作者：
Hinley, Jennifer;Duke, Rosalind;Jinks, Jessica;Stahlschmidt, Jens;Keene, David;Cervellione, Raimondo M.;Mushtaq, Imran;De Coppi, Paolo;Garriboli, Massimo;Southgate, Jennifer
膀胱外翻 (BEX) 是一种罕见的发育异常，导致膀胱板开放、暴露。尽管正常的膀胱尿路上皮是有丝分裂静止的屏障上皮，但 BEX 上皮的组织学研究报告了鳞状和增殖性变化，这些变化可以在手术闭合后持续存在。目前的研究检查了患者来源的 BEX 上皮细胞在体外是否能够在允许的条件下生成屏障形成上皮。从 11 个 BEX 样本中分离出上皮细胞，在组织学上分为移行细胞 (n = 6) 或鳞状细胞 (n = 5)，并在体外进行增殖。在有利于正常人尿路上皮细胞培养物形成分化的紧密屏障的条件下，11个BEX细胞系中的8个产生了超过1000Ω.cm2的跨上皮电阻，其中3个鳞状细胞系未能形成紧密屏障。鳞状 KRT14 转录物的表达与屏障发育之间存在负相关关系。尿路上皮分化的转录驱动因子 PPARG、GATA3 和 FOXA1 在鳞状 BEX 培养物中表现出表达减少。这些发现表明 BEX 中发现的向鳞状上皮表型过渡的尿路上皮转录程序的发育中断。 BEX 上皮表型的评估可以为管理和治疗策略提供信息，可逆性鳞状上皮与难治性鳞状上皮之间的区别可以识别有医疗并发症风险的患者或最适合重建组织工程策略的患者。
Bladder exstrophy (BEX) is a rare developmental abnormality resulting in an open, exposed bladder plate. Although normal bladder urothelium is a mitotically quiescent barrier epithelium, histologic studies of BEX epithelia report squamous and proliferative changes that can persist beyond surgical closure. The current study examined whether patient-derived BEX epithelial cells in vitro were capable of generating a barrier-forming epithelium under permissive conditions. Epithelial cells isolated from 11 BEX samples, classified histologically as transitional (n = 6) or squamous (n = 5), were propagated in vitro. In conditions conducive to differentiated tight barrier formation by normal human urothelial cell cultures, 8 of 11 BEX lines developed transepithelial electrical resistances of more than 1000 Ω.cm2, with 3 squamous lines failing to generate tight barriers. An inverse relationship was found between expression of squamous KRT14 transcript and barrier development. Transcriptional drivers of urothelial differentiation PPARG, GATA3, and FOXA1 showed reduced expression in squamous BEX cultures. These findings implicate developmental interruption of urothelial transcriptional programming in the spectrum of transitional to squamous epithelial phenotypes found in BEX. Assessment of BEX epithelial phenotype may inform management and treatment strategies, for which distinction between reversible versus intractably squamous epithelium could identify patients at risk of medical complications or those who are most appropriate for reconstructive tissue engineering strategies.
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