New therapy for chronic otitis media or sinusitis by controlling mucous cell metaplasia

我们证明了肠道粘液细胞发育的关键转录因子Math1显著增加了小鼠中耳粘膜中粘液样细胞的数量。Math1在促炎症细胞因子(TNFa)和上皮分化因子维甲酸(RA)存在的情况下，通过上调粘蛋白及其伴侣：三叶因子(TFFs)，在体外协同促进小鼠中耳上皮细胞向粘液样细胞分化。我们还证明，表皮生长因子受体酪氨酸激酶抑制剂AG1478可以抑制Math1的激活(转位到细胞核)。此外，AG1478还可抑制TNFa和RA诱导的粘液细胞化生。这些结果提示，Math1的调节可以预防慢性中耳炎的粘液细胞化生。

We demonstrated that Math1, a critical transcription factor for the development of mucous cells in the intestine, significantly increased the mucus-like cell numbers in the middle ear mucosa of mice. Math1, in the presence of pro-inflammatory cytokine (TNFa) and epithelial differentiation factor retinoic acid (RA), synergistically promoted the differentiation of mouse middle ear epithelial cells into mucus-like cells via upregulation of mucins and their chaperones:trefoil factors (TFFs) in vitro. We also demonstrated that Math1 activation (translocation to nucleus) was inhibited by epidermal growth factor receptor tyrosine kinase inhibitor, AG1478. In addition, mucous cell metaplasia induced by TNFa and RA was abrogated by AG1478. These results suggested that regulation of Math1 could prevent mucous cell metaplasia in chronic otitis media.