Family With Sequence Similarity 13 Member A Mediates Tgf-Beta 1-Induced Emt In Small Airway Epithelium Of Patients With Chronic Obstructive Pulmonary Disease

Background: To explore the role of family with sequence similarity 13 member A (FAM13A) in TGF-beta 1-induced EMT in the small airway epithelium of patients with chronic obstructive pulmonary disease (COPD).Methods: Small airway wall thickness and protein levels of airway remodeling markers, EMT markers, TGF-beta 1, 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-beta 1-induced EMT marker alterations in human bronchial epithelial cell line BEAS-2B.Results: 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 (alpha-SMA, vimentin, and N-cadherin), TGF-beta 1, 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-beta 1 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-beta 1-induced EMT marker protein alterations in BEAS-2B cells.Conclusions: FAM13A upregulation is associated with TGF-beta 1-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.