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Article: Regulation of blood-testis barrier dynamics: An in vivo study

TitleRegulation of blood-testis barrier dynamics: An in vivo study
Authors
Keywordsα2-Macroglobulin
Adherens junctions
Blood-testis barrier
p38 MAP kinase
TGF-β3
Tight junctions
Issue Date2004
PublisherCompany of Biologists Ltd.
Citation
Journal Of Cell Science, 2004, v. 117 n. 5, p. 783-798 How to Cite?
AbstractAn in vivo model was used to investigate the regulation of tight junction (TJ) dynamics in the testis when adult rats were treated with CdCl2. It was shown that the CdCl2-induced disruption of the blood-testis barrier (BTB) associated with a transient induction in testicular TGF-β2 and TGF-β3 (but not TGF-β1 and the phosphorylated p38 mitogen activated protein (MAP) kinase, concomitant with a loss of occludin and zonula occludens-1 (ZO-1) from the BTB site in the seminiferous epithelium. These results suggest that BTB dynamics in vivo are regulated by TGF-β2/-β3 via the p38 MAP kinase pathway. Indeed, SB202190, a specific p38 MAP kinase inhibitor, blocked the CdCl2-induced occludin and ZO-1 loss from the BTB. This result clearly illustrates that CdCl2 mediates its BTB disruptive effects via the TGF-β3/p38 MAP kinase signaling pathway. Besides, this CdCl2-induced occludin and ZO-1 loss from the BTB also associated with a significant loss of the cadherin/catenin and the nectin/afadin protein complexes at the site of cell-cell actin-based adherens junctions (AJs). An induction of α2-macroglobulin (a non-specific protease inhibitor) was also observed during BTB damage and when the seminiferous epithelium was being depleted of germ cells. These data illustrate that a primary disruption of the BTB can lead to a secondary loss of cell adhesion function at the site of AJs, concomitant with an induction in protease inhibitor, which apparently is used to protect the epithelium from unwanted proteolysis. α2-Macroglobulin was also shown to associate physically with TGF-β3, afadin and nectin 3, but not occludin, E-cadherin or N-cadherin, indicating its possible role in junction restructuring in vivo. Additionally, the use of SB202190 to block the TGF-β3/p-38 MAP kinase pathway also prevented the CdCl2-induced loss of cadherin/catenin and nectin/afadin protein complexes from the AJ sites, yet it had no apparent effect on α2-macroglobulin. These results demonstrate for the first time that the TGF-β3/p38 MAP kinase signaling pathway is being used to regulate both TJ and AJ dynamics in the testis, mediated by the effects of TGF-β3 on TJ- and AJ-integral membrane proteins and adaptors, but not protease inhibitors.
Persistent Identifierhttp://hdl.handle.net/10722/43520
ISSN
2015 Impact Factor: 4.706
2015 SCImago Journal Rankings: 3.501
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWong, CHen_HK
dc.contributor.authorMruk, DDen_HK
dc.contributor.authorLui, WYen_HK
dc.contributor.authorCheng, CYen_HK
dc.date.accessioned2007-03-23T04:47:50Z-
dc.date.available2007-03-23T04:47:50Z-
dc.date.issued2004en_HK
dc.identifier.citationJournal Of Cell Science, 2004, v. 117 n. 5, p. 783-798en_HK
dc.identifier.issn0021-9533en_HK
dc.identifier.urihttp://hdl.handle.net/10722/43520-
dc.description.abstractAn in vivo model was used to investigate the regulation of tight junction (TJ) dynamics in the testis when adult rats were treated with CdCl2. It was shown that the CdCl2-induced disruption of the blood-testis barrier (BTB) associated with a transient induction in testicular TGF-β2 and TGF-β3 (but not TGF-β1 and the phosphorylated p38 mitogen activated protein (MAP) kinase, concomitant with a loss of occludin and zonula occludens-1 (ZO-1) from the BTB site in the seminiferous epithelium. These results suggest that BTB dynamics in vivo are regulated by TGF-β2/-β3 via the p38 MAP kinase pathway. Indeed, SB202190, a specific p38 MAP kinase inhibitor, blocked the CdCl2-induced occludin and ZO-1 loss from the BTB. This result clearly illustrates that CdCl2 mediates its BTB disruptive effects via the TGF-β3/p38 MAP kinase signaling pathway. Besides, this CdCl2-induced occludin and ZO-1 loss from the BTB also associated with a significant loss of the cadherin/catenin and the nectin/afadin protein complexes at the site of cell-cell actin-based adherens junctions (AJs). An induction of α2-macroglobulin (a non-specific protease inhibitor) was also observed during BTB damage and when the seminiferous epithelium was being depleted of germ cells. These data illustrate that a primary disruption of the BTB can lead to a secondary loss of cell adhesion function at the site of AJs, concomitant with an induction in protease inhibitor, which apparently is used to protect the epithelium from unwanted proteolysis. α2-Macroglobulin was also shown to associate physically with TGF-β3, afadin and nectin 3, but not occludin, E-cadherin or N-cadherin, indicating its possible role in junction restructuring in vivo. Additionally, the use of SB202190 to block the TGF-β3/p-38 MAP kinase pathway also prevented the CdCl2-induced loss of cadherin/catenin and nectin/afadin protein complexes from the AJ sites, yet it had no apparent effect on α2-macroglobulin. These results demonstrate for the first time that the TGF-β3/p38 MAP kinase signaling pathway is being used to regulate both TJ and AJ dynamics in the testis, mediated by the effects of TGF-β3 on TJ- and AJ-integral membrane proteins and adaptors, but not protease inhibitors.en_HK
dc.format.extent2722090 bytes-
dc.format.extent25088 bytes-
dc.format.mimetypeapplication/pdf-
dc.format.mimetypeapplication/msword-
dc.languageengen_HK
dc.publisherCompany of Biologists Ltd.en_HK
dc.relation.ispartofJournal of Cell Scienceen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectα2-Macroglobulinen_HK
dc.subjectAdherens junctionsen_HK
dc.subjectBlood-testis barrieren_HK
dc.subjectp38 MAP kinaseen_HK
dc.subjectTGF-β3en_HK
dc.subjectTight junctionsen_HK
dc.subject.meshBlood-testis barrier - drug effects - physiology - ultrastructureen_HK
dc.subject.meshTestis - drug effects - metabolismen_HK
dc.subject.meshMap kinase signaling system - drug effectsen_HK
dc.subject.meshRats, sprague-dawleyen_HK
dc.subject.meshP38 mitogen-activated protein kinases - metabolismen_HK
dc.titleRegulation of blood-testis barrier dynamics: An in vivo studyen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0021-9533&volume=117&issue=pt 5&spage=783&epage=798&date=2004&atitle=Regulation+of+blood-testis+barrier+dynamics:+an+in+vivo+studyen_HK
dc.identifier.emailLui, WY: wylui@hku.hken_HK
dc.identifier.authorityLui, WY=rp00756en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1242/jcs.00900en_HK
dc.identifier.pmid14734653-
dc.identifier.scopuseid_2-s2.0-1342283974en_HK
dc.identifier.hkuros100787-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-1342283974&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume117en_HK
dc.identifier.issue5en_HK
dc.identifier.spage783en_HK
dc.identifier.epage798en_HK
dc.identifier.isiWOS:000189248400014-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridWong, CH=8849630400en_HK
dc.identifier.scopusauthoridMruk, DD=6701823934en_HK
dc.identifier.scopusauthoridLui, WY=35220192400en_HK
dc.identifier.scopusauthoridCheng, CY=7404797787en_HK
dc.identifier.citeulike5302558-

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