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Platelet‐derived growth factor mediates tight junction redistribution and increases permeability in MDCK cells
Author(s) -
Harhaj Nicole S.,
Barber Alistair J.,
Antonetti David A.
Publication year - 2002
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.10183
Subject(s) - occludin , microbiology and biotechnology , tight junction , platelet derived growth factor receptor , growth factor , biology , cell junction , paracellular transport , vascular permeability , cell , permeability (electromagnetism) , biochemistry , endocrinology , receptor , membrane
Increased tissue permeability is a common characteristic of a number of diseases such as pulmonary edema, inflammatory bowel disease, several kidney diseases, diabetic retinopathy, and tumors. We hypothesized that growth factors increase permeability by redistribution of tight junction proteins away from the cell border. To investigate mechanisms of growth factor‐mediated permeability, we examined the effect of platelet derived growth factor (PDGF) on Madin‐Darby canine kidney (MDCK) cell tight junction protein distribution and on permeability. PDGF altered the cellular distribution of occludin and ZO‐1 from the cell border to the cytoplasm and increased permeability to 70 kDa dextran in a concentration‐dependent manner. Treatment of MDCK cells with PDGF prior to fixation allowed binding of the lectin concanavalin A to the basement membrane of fixed cells, while binding was prevented in untreated control monolayers, implying that PDGF induced the formation of a paracellular transport pathway. Cell fractionation experiments with PDGF‐treated cells revealed a novel occludin‐containing low‐density, detergent resistant subcellular structure, which increased in the buoyant fractions relative to occludin in the pellet in a time‐ and concentration‐dependent manner. Immunocytochemistry revealed that a pool of internalized occludin co‐labels with the early endosome marker, EEA1, suggesting that PDGF may stimulate occludin to enter an endosomal pathway. PDGF may act as a permeabilizing agent by moving tight junction proteins away from the cell border in discrete microdomains, and the effects of PDGF on permeability and tight junction protein distribution may model the regulation of epithelial and endothelial barrier properties by other peptide growth factors. J. Cell. Physiol. 193: 349–364, 2002. © 2002 Wiley‐Liss, Inc.