Type IV collagen α6 chain is a regulator of keratin 10 in keratinization of oral mucosal epithelium.

Type IV collagen α6 chain is a regulator of keratin 10 in keratinization of oral mucosal epithelium.
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DOI:
10.1038/s41598-018-21000-0
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发表时间:
2018-02-08
期刊:
影响因子:
4.6
通讯作者:
Oohashi T
Oohashi T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Komori T;Ono M;Hara ES;Ueda J;Nguyen HTT;Nguyen HT;Yonezawa T;Maeba T;Kimura-Ono A;Takarada T;Momota R;Maekawa K;Kuboki T;Oohashi T

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口腔黏膜角化是维持牙龈组织健康的重要因素,了解口腔黏膜角化的机制对成功管理健康牙龈至关重要。先前的研究表明,基底膜在上皮细胞的增殖和分化中有很强的参与。因此,首先,为了鉴定角化粘膜特异性基底膜组分,在8周龄小鼠中进行IV型胶原的六条α链的免疫组织化学分析。在角化和非角化粘膜中没有观察到IV型胶原α 1(IV)和α 2(IV)链的表达模式的差异。然而,有趣的是,在角化粘膜中强烈检测到IV型胶原α 5(IV)和α 6(IV)链。为了分析IV型胶原亚型α 6(IV)在口腔粘膜角化中的功能作用,我们分析了Col4a6基因敲除小鼠。在新生的Col4a6基因敲除小鼠中观察到上皮发育延迟和低水平的KRT10。此外,使用人牙龈上皮细胞进行的功能丧失分析的体外实验证实了α 6(IV)链在上皮角化中的重要作用。这些发现表明,α 112:α 556(IV)网络是唯一包含α 6(IV)链的网络,是口腔粘膜上皮角化中KRT 10表达的调节因子之一。
Keratinized mucosa is of fundamental importance to maintain healthy gingival tissue, and understanding the mechanisms of oral mucosa keratinization is crucial to successfully manage healthy gingiva. Previous studies have shown a strong involvement of the basement membrane in the proliferation and differentiation of epithelial cells. Therefore, first, to identify the keratinized mucosa-specific basement membrane components, immunohistochemical analysis for the six alpha chains of type IV collagen was performed in 8-week-old mice. No difference in the expression pattern of type IV collagen α1(IV) and α2(IV) chains was observed in the keratinized and non-keratinized mucosa. Interestingly, however, type IV collagen α5(IV) and α6(IV) chains specifically were strongly detected in the keratinized mucosa. To analyze the functional roles of the type IV collagen isoform α6(IV) in oral mucosa keratinization, we analyzed Col4a6-knockout mice. Epithelial developmental delay and low levels of KRT10 were observed in new-born Col4a6-knockout mice. Additionally, in vitro experiments with loss-of function analysis using human gingival epithelial cells confirmed the important role of α6(IV) chain in epithelial keratinization. These findings indicate that α112:α556 (IV) network, which is the only network that includes the α6(IV) chain, is one regulator of KRT10 expression in keratinization of oral mucosal epithelium.
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