Abstract：
Asthma is a chronic inflammatory disease characterized by airway remodeling and lung inflammation. Collagen triple helix repeat containing 1 (CTHRC1), a glycoprotein, is involved in multiple pathological processes, including inflammation and fibrosis. However, the function of CTHRC1 in asthma remains unclear. In the present study, the mouse asthma model was successfully generated by sensitizing and challenging mice with ovalbumin (OVA). CTHRC1 expression at both RNA and protein levels was significantly upregulated in lung tissues of asthmatic mice. Asthmatic mice exhibited significant airway remodeling as evidenced by increased bronchial wall and smooth muscle cell layer thickness, goblet cell hyperplasia and collagen deposition, and epithelial-mesenchymal transition (EMT), but those characteristics were reversed by CTHRC1 silencing. The cell model with transforming growth factor-β1 (TGF-β1) induction in bronchial epithelial cells (BEAS-2B) was conducted to verify the effects of CTHRC1 on EMT, a classic mechanism that mediates airway remodeling. The results showed that TGF-β1 stimulation increased CTHRC1 expression, and CTHRC1 knockdown inhibited TGF-β1-induced EMT. OVA-treated mice also showed increased inflammatory cell infiltration and the production of OVA-specific immunoglobulin E (IgE), interleukin (IL)-4, IL-5, and IL-13, which were decreased by CTHRC1 downregulation. The effects of CTHRC1 on OVA-induced airway inflammation were further determined by treating BEAS-2B cells with IL-13, in which CTHRC1 knockdown reduced the IL-13-induced secretion of pro-inflammatory factors, including IL-4 and IL-5. In conclusion, these results indicate that CTHRC1 silencing attenuates asthmatic airway remodeling and inflammation in vivo and in vitro, suggesting that CTHRC1 may be a potential target for asthma treatment.
摘要：
哮喘是一种以气道重塑和肺部炎症为特征的慢性炎症性疾病。含有1个胶原三螺旋重复序列（CTHRC1），一种糖蛋白，参与多种病理过程，包括炎症和纤维化。然而,CTHRC1在哮喘中的作用尚不清楚.在本研究中,通过用卵清蛋白(OVA)致敏和攻击小鼠,成功建立了小鼠哮喘模型.在哮喘小鼠的肺组织中，RNA和蛋白质水平的CTHRC1表达均显着上调。哮喘小鼠表现出显著的气道重塑，表现为支气管壁和平滑肌细胞层厚度增加，杯状细胞增生和胶原沉积,和上皮-间质转化（EMT），但这些特征被CTHRC1沉默所逆转。用转化生长因子-β1（TGF-β1）诱导支气管上皮细胞（BEAS-2B）的细胞模型验证CTHRC1对EMT的影响。介导气道重塑的经典机制。结果显示TGF-β1刺激可增加CTHRC1的表达,CTHRC1敲低抑制TGF-β1诱导的EMT。OVA处理的小鼠还显示出增加的炎症细胞浸润和OVA特异性免疫球蛋白E（IgE）的产生，白细胞介素（IL）-4，IL-5和IL-13，通过CTHRC1下调而降低。通过IL-13处理BEAS-2B细胞进一步确定CTHRC1对OVA诱导的气道炎症的影响，其中CTHRC1敲低可减少IL-13诱导的促炎因子分泌，包括IL-4和IL-5。总之,这些结果表明，CTHRC1沉默在体内和体外减弱哮喘气道重塑和炎症，提示CTHRC1可能是哮喘治疗的潜在靶点。
