Coxsackievirus and adenovirus receptor is up-regulated in migratory germ cells during passage of the blood-testis barrier

Coxsackievirus and adenovirus receptor is up-regulated in migratory germ cells during passage of the blood-testis barrier
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DOI:
10.1210/en.2007-0359
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发表时间:
2007-11-01
期刊:
影响因子:
4.8
通讯作者:
Sollerbrant, Kerstin
Sollerbrant, Kerstin
中科院分区:
医学2区
文献类型:
--
作者:
Mirza, Momina;Petersen, Cecilia;Sollerbrant, Kerstin

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柯萨奇病毒和腺病毒受体(CAR)是一种细胞粘附分子,在上皮紧密连接和其他细胞-细胞接触中表达。采用间接免疫荧光、定量RT-PCR和Western blots检测CAR在发育和成年睾丸中的表达和分布。在围产期和产后发育过程中,CAR在支持细胞和生殖细胞中高度表达,随后mRNA和蛋白水平迅速下调。有趣的是,我们发现CAR是FSH的一个未知的下游靶点,因为在FSH刺激的Sertoli细胞的原代培养中诱导了CAR mRNA水平。与其他上皮细胞不同,CAR不是精系上皮紧密连接的一般组成部分,成年睾丸的支持细胞不表达CAR。相反,CAR的表达是阶段依赖的,并且特异性地在迁移生殖细胞中发现。RT-PCR还显示睾丸中存在连接粘附分子样(JAML)。其他人先前报道过JAML与CAR形成功能复合物,调节白细胞的经上皮迁移。JAML在睾丸中的表达表明,在生殖细胞穿越血睾丸屏障的迁移过程中可能存在类似的功能复合物。最后,鉴定了一个由car阳性迁移生殖细胞占据的中间室,其两侧有两个含occludin的连接。总之,这些结果暗示了在精子发生过程中,CAR在睾丸形态发生和生殖细胞穿过血睾丸屏障的迁移中的作用。
The coxsackievirus and adenovirus receptor (CAR) is a cell adhesion molecule expressed in epithelial tight junctions and other cell-cell contacts. Using indirect immunofluorescence, quantitative RT-PCR, and Western blots, the expression and distribution of CAR in developing and adult testis are examined. CAR is highly expressed in both Sertoli and germ cells during perinatal and postnatal development, followed by a rapid down-regulation of both mRNA and protein levels. Interestingly, we find that CAR is a previously unknown downstream target for FSH because CAR mRNA levels were induced in primary cultures of FSH-stimulated Sertoli cells. In contrast to other epithelia, CAR is not a general component of tight junctions in the seminiferous epithelium, and Sertoli cells in the adult testis do not express CAR. Instead, CAR expression is stage dependent and specifically found in migratory germ cells. RT-PCR also demonstrated the presence of junctional adhesion molecule-like (JAML) in the testis. JAML was previously reported by others to form a functional complex with CAR regulating transepithelial migration of leukocytes. The expression of JAML in the testis suggests that a similar functional complex might be present during germ cell migration across the blood-testis barrier. Finally, an intermediate compartment occupied by CAR-positive, migrating germ cells and flanked by two occludin-containing junctions is identified. Together, these results implicate a function for CAR in testis morphogenesis and in migration of germ cells across the blood-testis barrier during spermatogenesis.