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- Publisher Website: 10.1095/biolreprod.102.011387
- Scopus: eid_2-s2.0-0242500358
- PMID: 12606350
- WOS: WOS:000182589700017
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Article: Transforming growth factor β3 regulates the dynamics of sertoli cell tight junctions via the p38 mitogen-activated protein kinase pathway
Title | Transforming growth factor β3 regulates the dynamics of sertoli cell tight junctions via the p38 mitogen-activated protein kinase pathway |
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Authors | |
Keywords | Sertoli cells Signal transduction Spermatogenesis Testis Tight junction |
Issue Date | 2003 |
Publisher | Society 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? |
Abstract | Earlier 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 Identifier | http://hdl.handle.net/10722/178821 |
ISSN | 2023 Impact Factor: 3.1 2023 SCImago Journal Rankings: 1.022 |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
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dc.contributor.author | Lui, WY | en_US |
dc.contributor.author | Lee, WM | en_US |
dc.contributor.author | Cheng, CY | en_US |
dc.date.accessioned | 2012-12-19T09:49:56Z | - |
dc.date.available | 2012-12-19T09:49:56Z | - |
dc.date.issued | 2003 | en_US |
dc.identifier.citation | Biology Of Reproduction, 2003, v. 68 n. 5, p. 1597-1612 | en_US |
dc.identifier.issn | 0006-3363 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/178821 | - |
dc.description.abstract | Earlier 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.language | eng | en_US |
dc.publisher | Society for the Study of Reproduction. The Journal's web site is located at http://www.biolreprod.org/ | en_US |
dc.relation.ispartof | Biology of Reproduction | en_US |
dc.subject | Sertoli cells | - |
dc.subject | Signal transduction | - |
dc.subject | Spermatogenesis | - |
dc.subject | Testis | - |
dc.subject | Tight junction | - |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Blood-Testis Barrier - Drug Effects - Physiology | en_US |
dc.subject.mesh | Cell Separation | en_US |
dc.subject.mesh | Cells, Cultured | en_US |
dc.subject.mesh | Culture Media | en_US |
dc.subject.mesh | Enzyme Inhibitors - Pharmacology | en_US |
dc.subject.mesh | Germ Cells - Physiology | en_US |
dc.subject.mesh | Humans | en_US |
dc.subject.mesh | Immunoblotting | en_US |
dc.subject.mesh | Immunohistochemistry | en_US |
dc.subject.mesh | Male | en_US |
dc.subject.mesh | Mitogen-Activated Protein Kinases - Antagonists & Inhibitors - Physiology | en_US |
dc.subject.mesh | Rna, Messenger - Biosynthesis - Genetics | en_US |
dc.subject.mesh | Rats | en_US |
dc.subject.mesh | Rats, Sprague-Dawley | en_US |
dc.subject.mesh | Recombinant Proteins - Pharmacology | en_US |
dc.subject.mesh | Reverse Transcriptase Polymerase Chain Reaction | en_US |
dc.subject.mesh | Seminiferous Epithelium - Drug Effects - Physiology | en_US |
dc.subject.mesh | Sertoli Cells - Physiology | en_US |
dc.subject.mesh | Signal Transduction - Physiology | en_US |
dc.subject.mesh | Tight Junctions - Physiology | en_US |
dc.subject.mesh | Transforming Growth Factor Beta - Physiology | en_US |
dc.subject.mesh | Transforming Growth Factor Beta3 | en_US |
dc.subject.mesh | P38 Mitogen-Activated Protein Kinases | en_US |
dc.title | Transforming growth factor β3 regulates the dynamics of sertoli cell tight junctions via the p38 mitogen-activated protein kinase pathway | en_US |
dc.type | Article | en_US |
dc.identifier.email | Lui, WY: wylui@hku.hk | en_US |
dc.identifier.email | Lee, WM: hrszlwm@hku.hk | en_US |
dc.identifier.authority | Lui, WY=rp00756 | en_US |
dc.identifier.authority | Lee, WM=rp00728 | en_US |
dc.description.nature | link_to_subscribed_fulltext | en_US |
dc.identifier.doi | 10.1095/biolreprod.102.011387 | en_US |
dc.identifier.pmid | 12606350 | - |
dc.identifier.scopus | eid_2-s2.0-0242500358 | en_US |
dc.identifier.hkuros | 81233 | - |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-0242500358&selection=ref&src=s&origin=recordpage | en_US |
dc.identifier.volume | 68 | en_US |
dc.identifier.issue | 5 | en_US |
dc.identifier.spage | 1597 | en_US |
dc.identifier.epage | 1612 | en_US |
dc.identifier.isi | WOS:000182589700017 | - |
dc.publisher.place | United States | en_US |
dc.identifier.scopusauthorid | Lui, WY=35220192400 | en_US |
dc.identifier.scopusauthorid | Lee, WM=24799156600 | en_US |
dc.identifier.scopusauthorid | Cheng, CY=7404797787 | en_US |
dc.identifier.issnl | 0006-3363 | - |