Fibronectin synthesis, but not α-smooth muscle expression, is regulated by periostin in gingival healing through FAK/JNK signaling

在牙龈愈合过程中,纤维连接蛋白的合成(而非 α 平滑肌的表达)受骨膜蛋白通过 FAK/JNK 信号调控

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作者:Shawna S Kim, Georgia E Nikoloudaki, Sarah Michelsons, Kendal Creber, Douglas W Hamilton

Abstract

During skin healing, periostin facilitates myofibroblast differentiation through a β1 integrin/FAK dependent mechanism and continued expression is associated with scarring. In contrast to skin, gingival tissue does not typically scar upon injury, but the role of periostin in gingival healing has never been investigated. Using a rat gingivectomy model, we show that the gingival architecture is re-established within 14 days of wounding. Periostin mRNA levels peak at day 7 post-wounding, with persistence of periostin protein in the connective tissue through day 14. Collagen type I and lysyl oxidase mRNA levels peak at day 7 post wounding, which corresponded with the peak of fibroblast proliferation. Although α-smooth muscle actin mRNA levels increased 200-fold in the tissue, no myofibroblasts were detected in the regenerating tissue. In vitro, human gingival fibroblast adhesion on periostin, but not collagen, was inhibited by blocking β1 integrins. Fibroblasts cultured on periostin exhibited similar rates of proliferation and myofibroblast differentiation to cells cultured on collagen only. However, human gingival fibroblasts cultured in the presence of periostin exhibited significantly increased fibronectin and collagen mRNA levels. Increases in fibronectin production were attenuated by pharmacological inhibition of FAK and JNK signaling in human gingival fibroblasts. In vivo, mRNA levels for fibronectin peaked at day 3 and 7 post wounding, with protein immunoreactivity highest at day 7, suggesting periostin is a modulator of fibronectin production during gingival healing.

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