Polidocanol injury wildtype versus Myd88 KO trachea

Nf-kB activity is associated with the key pathological features of chronic respiratory diseases including epithelial remodelling, excess mucous production, and submucosal gland hyperplasia. However, the role of Nf-kB activity in airway epithelial differentiation remains controversial. In the present study we demonstrate that Nf-kB adaptor protein Myd88 deficiency promotes increased airway submucosal gland abundance and abnormal epithelial differentiation in proximal adult airways. Abnormal airway differentiation was not developmentally determined, became exacerbated following acute lung injury, and did not involve altered epithelial proliferation or apoptosis. Instead, we demonstrate that tracheal Myd88 deficiency promotes upregulation of a unique gene expression profile that includes activation of alternate, Myd88-independent Nf-kB signalling. Finally, we show that these effects are not intrinsically maintained in vitro using an air-liquid interface epithelial culture. This finding indicates that Myd88 deficiency promotes adult airway remodelling by regulating non-epithelial, non-cell autonomous Nf-kB activity. 20 microarray samples of whole trachea RNA in total: 5 samples wildtype control tissue 5 samples Myd88 KO control tissue 5 samples wildtype 3 day polidocanol injury tissue 5 samples Myd88 KO 3 day polidocanol injury tissue核因子κB（Nf-kB）活性与慢性呼吸系统疾病的关键病理特征密切相关，包括上皮重塑、黏液过度分泌及黏膜下腺体增生。然而，Nf-kB活性在气道上皮分化中的作用仍存在争议。本研究证实，Nf-kB衔接蛋白髓系分化初级应答基因88（Myd88）缺失会促进成年近端气道黏膜下腺体丰度升高，并引发异常上皮分化。该异常气道分化并非由发育因素决定，在急性肺损伤后会进一步加重，且未涉及上皮增殖或凋亡的改变。取而代之的是，本研究发现气管Myd88缺失会上调独特的基因表达谱，其中包括激活非依赖Myd88的替代性Nf-kB信号通路。最后，本研究显示，采用气液界面上皮培养模型无法在体外固有维持上述效应。这一结果表明，Myd88缺失通过调控非上皮、非细胞自主性的Nf-kB活性，促进成年气道重塑。本数据集共包含20份全气管RNA的微阵列（microarray）样本：5份野生型对照组织样本、5份Myd88基因敲除（KO）对照组织样本、5份野生型3天聚多卡醇（polidocanol）损伤组织样本，以及5份Myd88基因敲除3天聚多卡醇损伤组织样本。