File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Transforming growth factor β3 regulates the dynamics of sertoli cell tight junctions via the p38 mitogen-activated protein kinase pathway

TitleTransforming growth factor β3 regulates the dynamics of sertoli cell tight junctions via the p38 mitogen-activated protein kinase pathway
Authors
Issue Date2003
PublisherSociety for the Study of Reproduction. The Journal's web site is located at http://www.biolreprod.org/
Citation
Biology Of Reproduction, 2003, v. 68 n. 5, p. 1597-1612 How to Cite?
AbstractEarlier studies have implicated the significance of transforming growth factor-β3 (TGFβ3) in the regulation of Sertoli cell tight junction (TJ) dynamics, possibly via its inhibitory effects on the expression of occludin, claudin-11, and zonula occludens-1 (ZO-1). Yet the mechanism by which TGFβ3 regulates the Sertoli cell TJ-permeability barrier is not known. Using techniques of semiquantitative reverse transcription-PCR (RT-PCR), immunoblotting, immunohistochemistry, and inhibitors against different kinases coupled with physiological techniques to assess the Sertoli cell TJ barrier function, it was shown that this TGFβ3-induced effect on Sertoli cell TJ dynamics is mediated via the p38 mitogen-activated protein (MAP) kinase pathway. First, the assembly of the Sertoli cellTJ barrier was shown to be associated with a transient but significant decline in both the TGFβ3 production and expression by Sertoli cells. Furthermore, addition of TGFβ3 to Sertoli cell cultures during TJ assembly indeed perturbed the TJ barrier with an IC50 at ∼9 pM. Second, the TGFβ3-induced disruption of the TJ barrier was associated with a transient induction in MEKK2 but not the other upstream signaling molecules that mediate TGFβ3 action, such as Smad2, Cdc42, Rac2, and N-Ras, suggesting this effect might be mediated via the p38 MAP kinase pathway. This postulate was confirmed by the observation that TGFβ3 also induced the protein level of the activated and phosphorylated form of p38 MAP kinase at the time the TJ barrier was perturbed. Third, and perhaps the most important of all, this TGFβ3-mediated inhibitory effect on the TJ barrier and the TGFβ3-induced p-p38 MAP kinase production could be blocked by SB202190, a specific p38 MAP kinase inhibitor, but not U0126, a specific MEK1/2 kinase inhibitor. These results thus unequivocally demonstrate that TGFβ3 utilizes the p38 MAP kinase pathway to regulate Sertoli cell TJ dynamics.
Persistent Identifierhttp://hdl.handle.net/10722/178821
ISSN
2015 Impact Factor: 3.471
2015 SCImago Journal Rankings: 1.646
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLui, WYen_US
dc.contributor.authorLee, WMen_US
dc.contributor.authorCheng, CYen_US
dc.date.accessioned2012-12-19T09:49:56Z-
dc.date.available2012-12-19T09:49:56Z-
dc.date.issued2003en_US
dc.identifier.citationBiology Of Reproduction, 2003, v. 68 n. 5, p. 1597-1612en_US
dc.identifier.issn0006-3363en_US
dc.identifier.urihttp://hdl.handle.net/10722/178821-
dc.description.abstractEarlier studies have implicated the significance of transforming growth factor-β3 (TGFβ3) in the regulation of Sertoli cell tight junction (TJ) dynamics, possibly via its inhibitory effects on the expression of occludin, claudin-11, and zonula occludens-1 (ZO-1). Yet the mechanism by which TGFβ3 regulates the Sertoli cell TJ-permeability barrier is not known. Using techniques of semiquantitative reverse transcription-PCR (RT-PCR), immunoblotting, immunohistochemistry, and inhibitors against different kinases coupled with physiological techniques to assess the Sertoli cell TJ barrier function, it was shown that this TGFβ3-induced effect on Sertoli cell TJ dynamics is mediated via the p38 mitogen-activated protein (MAP) kinase pathway. First, the assembly of the Sertoli cellTJ barrier was shown to be associated with a transient but significant decline in both the TGFβ3 production and expression by Sertoli cells. Furthermore, addition of TGFβ3 to Sertoli cell cultures during TJ assembly indeed perturbed the TJ barrier with an IC50 at ∼9 pM. Second, the TGFβ3-induced disruption of the TJ barrier was associated with a transient induction in MEKK2 but not the other upstream signaling molecules that mediate TGFβ3 action, such as Smad2, Cdc42, Rac2, and N-Ras, suggesting this effect might be mediated via the p38 MAP kinase pathway. This postulate was confirmed by the observation that TGFβ3 also induced the protein level of the activated and phosphorylated form of p38 MAP kinase at the time the TJ barrier was perturbed. Third, and perhaps the most important of all, this TGFβ3-mediated inhibitory effect on the TJ barrier and the TGFβ3-induced p-p38 MAP kinase production could be blocked by SB202190, a specific p38 MAP kinase inhibitor, but not U0126, a specific MEK1/2 kinase inhibitor. These results thus unequivocally demonstrate that TGFβ3 utilizes the p38 MAP kinase pathway to regulate Sertoli cell TJ dynamics.en_US
dc.languageengen_US
dc.publisherSociety for the Study of Reproduction. The Journal's web site is located at http://www.biolreprod.org/en_US
dc.relation.ispartofBiology of Reproductionen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBlood-Testis Barrier - Drug Effects - Physiologyen_US
dc.subject.meshCell Separationen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshCulture Mediaen_US
dc.subject.meshEnzyme Inhibitors - Pharmacologyen_US
dc.subject.meshGerm Cells - Physiologyen_US
dc.subject.meshHumansen_US
dc.subject.meshImmunoblottingen_US
dc.subject.meshImmunohistochemistryen_US
dc.subject.meshMaleen_US
dc.subject.meshMitogen-Activated Protein Kinases - Antagonists & Inhibitors - Physiologyen_US
dc.subject.meshRna, Messenger - Biosynthesis - Geneticsen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Sprague-Dawleyen_US
dc.subject.meshRecombinant Proteins - Pharmacologyen_US
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen_US
dc.subject.meshSeminiferous Epithelium - Drug Effects - Physiologyen_US
dc.subject.meshSertoli Cells - Physiologyen_US
dc.subject.meshSignal Transduction - Physiologyen_US
dc.subject.meshTight Junctions - Physiologyen_US
dc.subject.meshTransforming Growth Factor Beta - Physiologyen_US
dc.subject.meshTransforming Growth Factor Beta3en_US
dc.subject.meshP38 Mitogen-Activated Protein Kinasesen_US
dc.titleTransforming growth factor β3 regulates the dynamics of sertoli cell tight junctions via the p38 mitogen-activated protein kinase pathwayen_US
dc.typeArticleen_US
dc.identifier.emailLui, WY: wylui@hku.hken_US
dc.identifier.emailLee, WM: hrszlwm@hku.hken_US
dc.identifier.authorityLui, WY=rp00756en_US
dc.identifier.authorityLee, WM=rp00728en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1095/biolreprod.102.011387en_US
dc.identifier.pmid12606350-
dc.identifier.scopuseid_2-s2.0-0242500358en_US
dc.identifier.hkuros81233-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0242500358&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume68en_US
dc.identifier.issue5en_US
dc.identifier.spage1597en_US
dc.identifier.epage1612en_US
dc.identifier.isiWOS:000182589700017-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridLui, WY=35220192400en_US
dc.identifier.scopusauthoridLee, WM=24799156600en_US
dc.identifier.scopusauthoridCheng, CY=7404797787en_US

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats