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ERK/CREB 和 p38 MAPK/MMP14 信号通路通过调节睾丸中连接蛋白的表达影响精子发生。

ERK/CREB and p38 MAPK/MMP14 Signaling Pathway Influences Spermatogenesis through Regulating the Expression of Junctional Proteins in Testis.

机构信息

The Sperm Laboratory, College of Life Sciences, Zhejiang University, Hangzhou 310058, China.

School of Medicine, Zhejiang University, Hangzhou 310003, China.

出版信息

Int J Mol Sci. 2024 Jul 4;25(13):7361. doi: 10.3390/ijms25137361.

Abstract

The hemolymph-testis barrier (HTB) is a reproduction barrier in Crustacea, guaranteeing the safe and smooth process of spermatogenesis, which is similar to the blood-testis barrier (BTB) in mammals. The MAPK signaling pathway plays an essential role in spermatogenesis and maintenance of the BTB. However, only a few studies have focused on the influence of MAPK on crustacean reproduction. In the present study, we knocked down and inhibited MAPK in . Increased defects in spermatogenesis were observed, concurrently with a damaged HTB. Further research revealed that es-MMP14 functions downstream of ERK and p38 MAPK and degrades junctional proteins (Pinin and ZO-1); es-CREB functions in the ERK cascade as a transcription factor of ZO-1. In addition, when es-MMP14 and es-CREB were deleted, the defects in HTB and spermatogenesis aligned with abnormalities in the MAPK. However, JNK impacts the integrity of the HTB by changing the distribution of intercellular junctions. In summary, the MAPK signaling pathway maintains HTB integrity and spermatogenesis through es-MMP14 and es-CREB, which provides insights into the evolution of gene function during barrier evolution.

摘要

血-睾屏障(HTB)是甲壳动物的一种生殖屏障,保障了精子发生的安全顺畅过程,这与哺乳动物的血-睾屏障(BTB)相似。MAPK 信号通路在精子发生和 BTB 的维持中起着至关重要的作用。然而,只有少数研究关注 MAPK 对甲壳动物生殖的影响。在本研究中,我们敲低和抑制了 MAPK,观察到精子发生缺陷增加,同时 HTB 受损。进一步的研究表明,es-MMP14 在 ERK 和 p38 MAPK 下游发挥作用,降解连接蛋白(Pinin 和 ZO-1);es-CREB 在 ERK 级联中作为 ZO-1 的转录因子发挥作用。此外,当 es-MMP14 和 es-CREB 缺失时,HTB 和精子发生的缺陷与 MAPK 的异常一致。然而,JNK 通过改变细胞间连接的分布影响 HTB 的完整性。总之,MAPK 信号通路通过 es-MMP14 和 es-CREB 维持 HTB 的完整性和精子发生,为了解基因功能在屏障进化过程中的进化提供了线索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/791e/11242087/df131693e9ad/ijms-25-07361-g001.jpg

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