期刊
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
卷 1849, 期 6, 页码 601-611出版社
ELSEVIER
DOI: 10.1016/j.bbagrm.2015.03.005
关键词
Cell junction; JAM-B; Cytokine; TGF-beta; Spermatogenesis
资金
- Hong Kong Research Grants Council [HKU774213]
- HKU/CRCG
Junctional adhesion molecule-B (JAM-B) is found between Sertoli cells at the blood-testis barrier (BIB) as well as between Sertoli and germ cells at the apical ectoplasmic specializations (ES) in the testis. The expression of JAM-B is tightly regulated to modulate the passage of spermatocytes across the BTB as well as the release of mature spermatozoa from the seminiferous epithelium. Transforming growth factor beta (TGF-beta) family is implicated in the regulation of testicular cell junction dynamics during spermatogenesis. This study aims to investigate the effects of TGF-beta 3 on the expression of JAM-B as well as the underlying mechanisms on how TGF-beta 3 regulates JAM-B expression to facilitate the disassembly of the BIB and apical ES. Our results revealed that TGF-beta 3 suppresses JAM-B at post-transcriptional and post-translational levels. Inhibitor, siRNA knockdown and co-immunoprecipitation have shown that TGF-beta 3 induces JAM-B protein degradation via ubiquitin-proteasome pathway. Immunofluorescence staining further confirmed that blockage of ubiquitin-proteasome pathway could abrogate TGF-beta 3-induced loss of JAM-B at the cell-cell interface. siRNA knockdown and immunofluorescence staining also demonstrated that activation of Smad signaling is required for TGF-beta 3-induced JAM-B protein degradation. In addition, TGF-beta 3 reduces JAM-B mRNA levels, at least in part, via post-transcriptional regulation. mRNA stability assay has confirmed that TGF-beta 3 promotes the degradation of JAM-B transcript and TGF-beta 3-mediated mRNA destabilization requires the activation of ERK1/2 and p54 JNK signal cascades. Taken together, TGF-beta 3 significantly downregulates JAM-B expression via post-transcriptional and post-translational modulation and results in the disruption of BTB and apical ES. (C) 2015 Elsevier B.V. All rights reserved.
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