Blood-Testis Barrier Dynamics Are Regulated by α2-Macroglobulin via the c-Jun N-Terminal Protein Kinase Pathway

作者: Ching-hang Wong , Dolores D. Mruk , Michelle K. Y. Siu , C. Yan Cheng

DOI: 10.1210/EN.2004-1464

关键词:

摘要: The blood-testis barrier (BTB), in contrast to the blood-brain and blood-retina barriers, is composed of coexisting tight junctions, gap basal ectoplasmic specializations, a testis-specific type adherens junction. Recent studies showed that BTB restructuring facilitates germ cell migration during spermatogenesis involves proteolysis, an event usually restricted cell-matrix interface other epithelia. For instance, surge alpha(2)-macroglobulin (alpha(2)-MG), protease inhibitor produced by Sertoli cells, was detected at Sertoli-Sertoli Sertoli-germ epithelium cadmium chloride-induced disruption adult rats. It thus proposed increase alpha(2)-MG crucial for protecting from unwanted proteolysis as well regulating availability cytokines affect junction turnover. Although both dynamics are regulated via p38 MAPK signaling pathway, mechanism(s) regulates entirely unknown. In this study, we have shown administering dimethylaminopurine, c-Jun N-terminal protein kinase (JNK) inhibitor, testis, JNK activity blocked specifically production inhibited, worsening damage epithelium. Studies coupled with inhibitors, immunoblottings, immunofluorescent electron microscopy unequivocally demonstrated pathway putative regulatory testis. This finding illustrates first time occurs normal physiology cell-cell highlighting significance regulation function.

参考文章(48)
Dolores D. Mruk, Michelle K.Y. Siu, Anne M. Conway, Nikki P.Y. Lee, Ann S.N. Lau, C. Yan Cheng, Role of Tissue Inhibitor of Metalloproteases‐1 in Junction Dynamics in the Testis Journal of Andrology. ,vol. 24, pp. 510- 523 ,(2003) , 10.1002/J.1939-4640.2003.TB02703.X
M D O'Connor-McCourt, L M Wakefield, Latent transforming growth factor-beta in serum. A specific complex with alpha 2-macroglobulin. Journal of Biological Chemistry. ,vol. 262, pp. 14090- 14099 ,(1987) , 10.1016/S0021-9258(18)47909-4
D L Shi, C Savona, J Gagnon, C Cochet, E M Chambaz, J J Feige, Transforming growth factor-beta stimulates the expression of alpha 2-macroglobulin by cultured bovine adrenocortical cells. Journal of Biological Chemistry. ,vol. 265, pp. 2881- 2887 ,(1990) , 10.1016/S0021-9258(19)39883-7
L Sottrup-Jensen, Alpha-macroglobulins: structure, shape, and mechanism of proteinase complex formation. Journal of Biological Chemistry. ,vol. 264, pp. 11539- 11542 ,(1989) , 10.1016/S0021-9258(18)80094-1
Lieve Umans, Lutgarde Serneels, Lut Overbergh, Lou Stas, Fred Van Leuven, α2-Macroglobulin- and Murinoglobulin-1- Deficient Mice : A Mouse Model for Acute Pancreatitis American Journal of Pathology. ,vol. 155, pp. 983- 993 ,(1999) , 10.1016/S0002-9440(10)65198-X
W Northemann, M Heisig, D Kunz, P C Heinrich, Molecular cloning of cDNA sequences for rat alpha 2-macroglobulin and measurement of its transcription during experimental inflammation. Journal of Biological Chemistry. ,vol. 260, pp. 6200- 6205 ,(1985) , 10.1016/S0021-9258(18)88957-8
D. Mruk, J. Grima, W. M. Lee, L.-J. Zhu, C. Y. Cheng, C. C. S. Wong, S. S. W. Chung, S. S. W. Chung, Changes in the Expression of Junctional and Nonjunctional Complex Component Genes When Inter‐Sertoli Tight Junctions Are Formed In Vitro Journal of Andrology. ,vol. 21, pp. 227- 237 ,(2000) , 10.1002/J.1939-4640.2000.TB02100.X