Claudin-11 is over-expressed and dislocated from the blood-testis barrier in Sertoli cells associated with testicular intraepithelial neoplasia in men
Claudin-11 is over-expressed and dislocated from the blood-testis barrier in Sertoli cells associated with testicular intraepithelial neoplasia in men
复制标题
DOI：
10.1007/s00418-009-0576-2
复制
发表时间：
2009-06-01
影响因子：
2.3
通讯作者：
Brehm, Ralph
中科院分区：
文献类型：
--
作者：
Fink, Cornelia;Weigel, Roswitha;Brehm, Ralph
在小鼠睾丸中，claudin-11负责形成血-睾丸屏障（BTB）的特定平行TJ链。关于人BTB，没有关于跨膜TJ蛋白的信息。我们最近证明了睾丸上皮内瘤变（TIN）中BTB功能完整性的丧失，与外周TJ蛋白ZO-1和ZO-2的脱位相关。在这里，我们确定了密蛋白-11在人类BTB的表达和分布在生精小管与正常精子发生（NSP）和TIN。claudin-11的免疫染色显示在具有NSP的生精上皮中的基底BTB区域有强信号。在TIN小管内，claudin-11免疫染色变为弥漫性和细胞质。双免疫金标记证实了claudin-11和ZO-1在支持细胞间连接处的共定位。激光显微切割肾小管的实时RT-PCR显示TIN中claudin-11 mRNA表达上调。此外，通过Western印迹观察到增加的claudin-11蛋白。我们得出结论，claudin-11构成了TJ蛋白在人类BTB。在TIN小管中，claudin-11被上调并从BTB移位。因此，BTB的破坏与claudin-11的功能障碍有关，而与其表达失败无关。
In mouse testis, claudin-11 is responsible for the formation of specific parallel TJ strands of the blood-testis barrier (BTB). Concerning the human BTB, there is no information about the transmembrane TJ proteins. We recently demonstrated the loss of functional integrity of the BTB in testicular intraepithelial neoplasia (TIN), associated with a dislocation of the peripheral TJ proteins ZO-1 and ZO-2. Here, we determined the expression and distribution of claudin-11 at the human BTB in seminiferous tubules with normal spermatogenesis (NSP) and TIN. Immunostaining of claudin-11 revealed intense signals at the basal BTB region in seminiferous epithelium with NSP. Within TIN tubules, claudin-11 immunostaining became diffuse and cytoplasmic. Double immunogold labeling demonstrated a co-localization of claudin-11 and ZO-1 at the inter-Sertoli cell junctions. Real-time RT-PCR of laser microdissected tubules showed an up-regulation of claudin-11 mRNA in TIN. Additionally, increased claudin-11 protein was observed by Western blot. We conclude that claudin-11 constitutes a TJ protein at the human BTB. In TIN tubules, claudin-11 is up-regulated and dislocated from the BTB. Therefore, the disruption of the BTB is related to a dysfunction of claudin-11 and not to a failure of its expression.