To explore the role of family with sequence similarity 13 member A (FAM13A) in TGF-β1-induced EMT in the small airway epithelium of patients with chronic obstructive pulmonary disease (COPD). Small airway wall thickness and protein levels of airway remodeling markers, EMT markers, TGF-β1, and FAM13A were measured in lung tissue samples from COPD and non-COPD patients. The correlations of FAM13A expression with COPD severity and EMT marker expression were evaluated. Gain- and loss-of-function assays were performed to explore the functions of FAM13A in cell proliferation, motility, and TGF-β1-induced EMT marker alterations in human bronchial epithelial cell line BEAS-2B. Independent of smoking status, lung tissue samples from COPD patients exhibited significantly increased small airway thickness and collagen fiber deposition, along with enhanced protein levels of remodeling markers (collagen I, fibronectin, and MMP-9), mesenchymal markers (α-SMA, vimentin, and N-cadherin), TGF-β1, and FAM13A, compared with those from non-COPD patients. FAM13A expression negatively correlated with FEV1% and PO2 in COPD patients. In small airway epithelium, FAM13A expression negatively correlated with E-cadherin protein levels and positively correlated with vimentin protein levels. In BEAS-2B cells, TGF-β1 dose-dependently upregulated FAM13A protein levels. FAM13A overexpression significantly promoted cell proliferation and motility in BEAS-2B cells, whereas FAM13A silencing showed contrasting results. Furthermore, FAM13A knockdown partially reversed TGF-β1-induced EMT marker protein alterations in BEAS-2B cells. FAM13A upregulation is associated with TGF-β1-induced EMT in the small airway epithelium of COPD patients independent of smoking status, serving as a potential therapeutic target for anti-EMT therapy in COPD.

中文翻译：

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具有序列相似性的家族13个成员A介导慢性阻塞性肺疾病患者小气道上皮中TGF-β1诱导的EMT

探讨具有序列相似性的家族13成员A（FAM13A）在TGF-β1诱导的慢性阻塞性肺疾病（COPD）患者小气道上皮EMT中的作用。在 COPD 和非 COPD 患者的肺组织样本中测量了小气道壁厚度和气道重塑标志物、EMT 标志物、TGF-β1 和 FAM13A 的蛋白质水平。评估 FAM13A 表达与 COPD 严重程度和 EMT 标志物表达的相关性。进行了功能获得和功能丧失测定以探索 FAM13A 在细胞增殖、运动和 TGF-β1 诱导的人支气管上皮细胞系 BEAS-2B 中 EMT 标志物改变中的功能。与吸烟状况无关，COPD 患者的肺组织样本显示出显着增加的小气道厚度和胶原纤维沉积，以及与非 COPD 患者相比，重塑标志物（胶原蛋白 I、纤连蛋白和 MMP-9）、间充质标志物（α-SMA、波形蛋白和 N-钙粘蛋白）、TGF-β1 和 FAM13A 的蛋白质水平增强. FAM13A 表达与 COPD 患者的 FEV1% 和 PO2 呈负相关。在小气道上皮中，FAM13A 表达与 E-cadherin 蛋白水平呈负相关，与波形蛋白水平呈正相关。在 BEAS-2B 细胞中，TGF-β1 剂量依赖性地上调 FAM13A 蛋白水平。FAM13A 过表达显着促进了 BEAS-2B 细胞的细胞增殖和运动，而 FAM13A 沉默显示出相反的结果。此外，FAM13A 敲低部分逆转了 BEAS-2B 细胞中 TGF-β1 诱导的 EMT 标记蛋白改变。