Document Detail

Transforming growth factor beta 1 induces tight junction disruptions and loss of transepithelial resistance across porcine vas deferens epithelial cells.
MedLine Citation:
PMID:  21957188     Owner:  NLM     Status:  MEDLINE    
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.
Fernando Pierucci-Alves; Sheng Yi; Bruce D Schultz
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-02-14
Journal Detail:
Title:  Biology of reproduction     Volume:  86     ISSN:  1529-7268     ISO Abbreviation:  Biol. Reprod.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-16     Completed Date:  2012-07-09     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  United States    
Other Details:
Languages:  eng     Pagination:  36     Citation Subset:  IM    
Department of Anatomy and Physiology, Kansas State University, Manhattan, 66506, USA.
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MeSH Terms
Cell Membrane Permeability / drug effects*,  physiology
Cells, Cultured
Claudins / metabolism
Electrophysiological Phenomena
Epithelial Cells / drug effects*,  physiology
Membrane Proteins / metabolism
Mitogen-Activated Protein Kinase 11 / antagonists & inhibitors
Models, Animal
Patch-Clamp Techniques
Tight Junctions / drug effects*,  metabolism
Transforming Growth Factor beta1 / pharmacology*
Vas Deferens / cytology*
Grant Support
Reg. No./Substance:
0/Claudins; 0/Membrane Proteins; 0/OCLN protein, human; 0/Occludin; 0/Transforming Growth Factor beta1; EC Protein Kinase 11

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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