Math1, retinoic acid, and TNF-α synergistically promote the differentiation of mucous cells in mouse middle ear epithelial cells in vitro.

Math1, retinoic acid, and TNF-α synergistically promote the differentiation of mucous cells in mouse middle ear epithelial cells in vitro.
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DOI:
10.1038/pr.2013.103
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发表时间:
2013-09
期刊:
影响因子:
3.6
通讯作者:
Lin, Jizhen
Lin, Jizhen
中科院分区:
医学3区
文献类型:
--
作者:
Nakamura, Yoshihisa;Komori, Masahiro;Yamakawa, Kazuhiro;Hamajima, Yuki;Suzuki, Motohiko;Kim, Youngki;Lin, Jizhen

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中耳炎(OM)的一个关键问题是中耳粘膜中的粘液细胞化生,这是中耳粘膜中粘液过度产生和慢性OM发展的条件。然而,很少有人知道的驱动力的分化粘液细胞在OM。本研究以小鼠中耳上皮细胞(mMEEC)为研究对象,探讨Math1(一种对肠粘液细胞发育至关重要的转录因子)是否与炎性细胞因子(肿瘤坏死因子α,TNFα)和其他上皮分化因子(维甲酸,RA)协同诱导mMEEC体外分化为粘液样细胞。同时,将Math1转导到中耳粘膜中,观察其是否在体内诱导粘液细胞增生。Math1显著增加小鼠中耳粘膜中的粘液细胞数量。在TNFα和上皮分化因子视黄酸(RA)存在下,Math1通过上调粘蛋白及其伴侣三叶因子(TFFs)协同促进mMEEC向粘液样细胞的分化。RA处理12小时激活Math1,尽管单独RA对粘液样细胞分化的影响非常有限。在TNFα和RA存在的情况下,Math1通过诱导粘液细胞分化在OM的发病机制中起关键作用。
A key issue in otitis media (OM) is mucous cell metaplasia in the middle ear mucosa, a condition for hyperproduction of mucus in the middle ear mucosa and development of chronic OM. However, little is known about the driving force for the differentiation of mucous cells in OM. Mouse middle ear epithelial cells (mMEEC) were used in this study to test whether Math1, a critical transcription factor for the development of mucous cells in the intestine, synergize with inflammatory cytokines (tumor necrotic factor alpha, TNFα) and other epithelial differentiation factors (retinoid acid, RA) to induce the differentiation of mMEEC into mucus-like cells in vitro. Simultaneously, Math1 was transduced into the middle ear mucosa and see whether it induces mucous cell hyperplasia in vivo. Math1 significantly increased the mucus cell numbers in the middle ear mucosa of mice. Math1, in the presence of TNFα and epithelial differentiation factor retinoic acid (RA), synergistically promoted the differentiation of mMEEC into mucus-like cells via upregulation of mucins and their chaperones:trefoil factors (TFFs) in vitro. RA treatment for 12 hours activated Math1 although RA alone had very limited effects on mucus-like cell differentiation. Math1 plays a critical role in the pathogenesis of OM by induction of mucous cell differentiation, in the presence of TNFα and RA.
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