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Autocrine Production of Insulin-like Growth Factor-I (IGF-I) Affects Paracellular Transport Across Epithelial Cells In Vitro

机译:胰岛素样生长因子-I(IGF-I)的自分泌产生影响跨上皮细胞的细胞旁运输。

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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.
机译:自分泌分泌生长因子可对细胞活性产生重大影响。我们首次报道胰岛素样生长因子-I(IGF-I)的自分泌生产改变了体外牛乳腺上皮细胞的旁细胞转运。通过测量跨亲代乳腺上皮细胞的乳腺肺泡细胞-大T抗原(MAC-T细胞)中酚红的转运来评估细胞旁转运,将其培养在多孔膜上,并与组成性分泌IGF-的两种不同的转染MAC-T细胞系进行比较一世。六天后,亲代细胞培养中酚红的转运基本上被阻断,而分泌IGF-1的细胞基本上没有提供屏障。令人惊讶地,亲本和分泌IGF-I的细胞之间的共培养研究或添加外源性IGF-I或IGF-结合蛋白-3均未改变酚红转运性质。然而,分泌IGF-I的细胞确实比亲代细胞表达更低水平的连接成分occludin和E-cadherin,这表明局部自分泌IGF-I活性可能通过紧密连接蛋白和粘附连接蛋白水平的变化导致通透性增加。

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