Autocrine production of insulin-like growth factor-I (IGF-I) affects paracellular transport across epithelial cells in vitro.
Autocrine production of growth factors can have significant effects on cell activity. We report for the first time that autocrine production of insulin-like growth factor-I (IGF-I) alters paracellular transport across bovine mammary epithelial cells in vitro. Paracellular transport was assessed by measuring phenol red transport across mammary alveolar cells-large T antigen (MAC-T cells) derived from parental mammary epithelial cells, cultured on porous membranes and compared with two different transfected MAC-T cell lines that constitutively secrete IGF-I. Phenol red transport was essentially blocked in parental cell culture after six days, while IGF-I secreting cells provided essentially no barrier. Surprisingly, neither co-culture studies between parental and IGF-I-secreting cells nor addition of exogenous IGF-I or IGF-binding protein-3 reversed the phenol red transport properties. IGF-I-secreting cells did however express lower levels of the junction components occludin and E-cadherin than parental cells, suggesting that localized autocrine IGF-I activity might lead to increased permeability via changes in both the tight and adherens junction protein levels.
Department of Chemical Engineering, Virginia Polytechnic Institute and State University, Blacksburg 24061, Virginia, USA.
Julie M D
JM
Paye
R Michael
RM
Akers
William R
WR
Huckle
Kimberly
K
Forsten-Williams
D022005:Adherens Junctions / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects; D001692:Biological Transport / Q000187:drug effects; D002417:Cattle; D002452:Cell Count; D002478:Cells, Cultured; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D019899:Paracrine Communication / Q000187:drug effects; D010637:Phenolsulfonphthalein / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism
D018972:Insulin-Like Growth Factor Binding Protein 3; D008565:Membrane Proteins; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D010637:Phenolsulfonphthalein