| Transforming growth factor beta 1 induces tight junction disruptions and loss of transepithelial resistance across porcine vas deferens epithelial cells. | |
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MedLine Citation:
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PMID: 21957188 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Epithelial cells lining the male excurrent duct contribute to male fertility by employing a number of physiological mechanisms that generate a luminal microenvironment conducive to spermatozoa maturation and storage. Among these mechanisms, male duct epithelia establish intercellular tight junctions that constitute a barrier to paracellular diffusion of water, solutes, large molecules, and cells. Mechanisms regulating the male duct epithelial barrier remain unidentified. Transforming growth factor beta (TGFB) is a regulatory cytokine present in high concentrations in human semen. This study examined whether TGFB has any effects on epithelial function exhibited by primary cultures of porcine vas deferens epithelia. TGFB1 exposure caused a 70%-99% decrease in basal transepithelial electrical resistance (R(TE), a sensitive indicator of barrier integrity), while a significant decrease in anion secretory response to forskolin was detected at the highest levels of TGFB1 exposure employed. SB431542, a selective TGFB receptor I (TGFBR1) inhibitor, prevented decreases in barrier function. Results also demonstrated that TGFB1 exposure modifies the distribution pattern of tight junction proteins occludin and claudin 7. TGFBR1 is localized at the apical border of the native porcine vas deferens epithelium. Pharmacological inhibition of mitogen-activated protein kinase (MAPK) 11 (also known as p38-MAPK) did not alter the effect of TGFB1 on R(TE) significantly. These data suggest that epithelia lining the vas deferens are subject to disruptions in the physical barrier if active TGFB becomes bioavailable in the luminal fluid, which might be expected to compromise fertility. |
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Authors:
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Fernando Pierucci-Alves; Sheng Yi; Bruce D Schultz |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2012-02-14 |
Journal Detail:
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Title: Biology of reproduction Volume: 86 ISSN: 1529-7268 ISO Abbreviation: Biol. Reprod. Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-02-16 Completed Date: 2012-07-09 Revised Date: 2013-04-08 |
Medline Journal Info:
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Nlm Unique ID: 0207224 Medline TA: Biol Reprod Country: United States |
Other Details:
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Languages: eng Pagination: 36 Citation Subset: IM |
Affiliation:
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Department of Anatomy and Physiology, Kansas State University, Manhattan, 66506, USA. falves@vet.ksu.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Membrane Permeability / drug effects*, physiology Cells, Cultured Claudins / metabolism Electrophysiological Phenomena Epithelial Cells / drug effects*, physiology Male Membrane Proteins / metabolism Mitogen-Activated Protein Kinase 11 / antagonists & inhibitors Models, Animal Occludin Patch-Clamp Techniques Swine Tight Junctions / drug effects*, metabolism Transforming Growth Factor beta1 / pharmacology* Vas Deferens / cytology* |
| Grant Support | |
ID/Acronym/Agency:
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HD058398/HD/NICHD NIH HHS; R01 HD058398/HD/NICHD NIH HHS; RR017686/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Claudins; 0/Membrane Proteins; 0/OCLN protein, human; 0/Occludin; 0/Transforming Growth Factor beta1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 11 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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