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间隙连接蛋白 43 是细胞增殖的检查点成分,与多种人类睾丸疾病有关。

Connexin 43 a check-point component of cell proliferation implicated in a wide range of human testis diseases.

机构信息

Department of Urology, Pasteur Hospital, Nice, France.

出版信息

Cell Mol Life Sci. 2013 Apr;70(7):1207-20. doi: 10.1007/s00018-012-1121-3. Epub 2012 Aug 24.

Abstract

Gap junction channels link cytoplasms of adjacent cells. Connexins, their constitutive proteins, are essential in cell homeostasis and are implicated in numerous physiological processes. Spermatogenesis is a sophisticated model of germ cell proliferation, differentiation, survival, and apoptosis, in which a connexin isotype, connexin 43, plays a crucial role as evidenced by genomic approaches based on gene deletion. The balance between cell proliferation/differentiation/apoptosis is a prerequisite for maintaining levels of spermatozoa essential for fertility and for limiting anarchic cell proliferation, a major risk of testis tumor. The present review highlights the emerging role of connexins in testis pathogenesis, focusing specifically on two intimately interconnected human testicular diseases (azoospermia with impaired spermatogenesis and testicular germ cell tumors), whose incidence increased during the last decades. This work proposes connexin 43 as a potential cancer diagnostic and prognostic marker, as well as a promising therapeutic target for testicular diseases.

摘要

缝隙连接通道连接相邻细胞的细胞质。连接蛋白是其组成蛋白,对于细胞内环境稳定至关重要,并参与许多生理过程。精子发生是一种复杂的生殖细胞增殖、分化、存活和凋亡模式,基于基因缺失的基因组方法证实,连接蛋白同种型连接蛋白 43 起着关键作用。细胞增殖/分化/凋亡之间的平衡是维持精子数量所必需的,精子数量对于生育能力至关重要,并限制了睾丸肿瘤的主要风险——异常细胞增殖。本综述强调了连接蛋白在睾丸发病机制中的新作用,特别关注两种密切相关的人类睾丸疾病(生精障碍导致的无精子症和睾丸生殖细胞肿瘤),这两种疾病在过去几十年中的发病率有所增加。这项工作提出连接蛋白 43 可以作为睾丸疾病的潜在诊断和预后标志物,以及有希望的治疗靶点。

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