Glucocorticoid induced transcript 1 represses airway remodeling of asthmatic mouse via inhibiting IL-13/periostin/TGF-beta 1 signaling
Glucocorticoid induced transcript 1 represses airway remodeling of asthmatic mouse via inhibiting IL-13/periostin/TGF-beta 1 signaling
复制标题
糖皮质激素诱导的转录物 1 通过抑制 IL-13/骨膜素/TGF-β 1 信号传导抑制哮喘小鼠的气道重塑
DOI：
10.1016/j.intimp.2021.107637
复制
发表时间：
2021
影响因子：
5.6
通讯作者：
Guofeng Zhu
中科院分区：
文献类型：
--
作者：
Qiufen Xun;Jiulong Kuang;Qing Yang;Wei Wang;Guofeng Zhu
哮喘的特征是气道重塑。糖皮质激素诱导的转录本1（Glucocorticoid induced transcript 1，GLCCI 1）与哮喘的发生发展有关，但其确切机制尚不清楚。本研究采用卵清蛋白（OVA）联合氢氧化铝（Al 2 O3）建立小鼠哮喘模型。ELISA法测定支气管肺泡灌洗液和血清中炎性因子的浓度。采用H&E染色和Masson染色观察肺组织病理变化和胶原沉积情况。蛋白质印迹法检测蛋白质表达，qRT-PCR法检测GLCCI 1 mRNA的表达。在这里，我们证明了哮喘小鼠中OVA诱导的炎症、肺结构重塑和胶原沉积通过氢化泼尼松治疗或GLCCI 1过表达而显著改善。哮喘小鼠肺组织GLCCI 1表达降低，IL-13、periostin和TGF-β1表达升高。更重要的是，GLCCI 1的上调抑制了IL-13、骨膜蛋白和TGF-β1的表达，抑制了Smad 2和Smad 3的磷酸化以及细胞外基质（ECM）沉积相关蛋白的表达。IL-13诱导的气道上皮细胞（AECs）骨膜蛋白和TGF-β1表达上调、Smad 2和Smad 3磷酸化以及ECM沉积受GLCCI 1升高的抑制。此外，我们的研究结果表明，GLCCI 1的过表达通过抑制periostin表达来抑制IL-13对AECs的作用。总之，GLCCI 1通过抑制IL-13/periostin/TGF-β1信号通路抑制哮喘小鼠气道重塑。我们的数据为哮喘治疗提供了一个新的靶点。
Asthma is characterized by airway remodeling. Glucocorticoid induced transcript 1 (GLCCI1) was reported to be associated with the development of asthma, while its exact mechanism is still not clear. In our study, ovalbumin (OVA) combined with aluminum hydroxide were used to establish asthmatic mouse model. ELISA assay was fulfilled to ensure the concentration of inflammatory factors in both bronchoalveolar lavage fluid and serum. The pathological changes and collagen deposition in lung tissues were analyzed using H&E staining and Masson staining, respectively. The expression of proteins was measured using western blot, and the expression of GLCCI1 mRNA was ensured by qRT-PCR. Here, we demonstrated that OVA-induced inflammation, lung structural remodeling and collagen deposition in asthmatic mice was notably improved by hydroprednisone treatment or GLCCI1 overexpressing. The expression of GLCCI1 was decreased, while IL-13, periostin and TGF-β1 were increased in the lung tissue of asthmatic mice. Importantly, upregulation of GLCCI1 suppressed the expression of IL-13, periostin and TGF-β1, phosphorylation of Smad2 and Smad3, and extracellular matrix (ECM) deposition-related proteins expression. IL-13-induced upregulation of periostin and TGF-β1 expression, phosphorylation of Smad2 and Smad3, and ECM deposition in airway epithelial cells (AECs) was repressed by GLCCI1 increasing. Furthermore, our results showed that overexpression of GLCCI1 repressed the effect of IL-13 on AECs via inhibiting periostin expression. Overall, our data revealed that GLCCI1 limited the airway remodeling in mice with asthma through inhibiting IL-13/periostin/TGF-β1 signaling pathway. Our data provided a novel target for asthma treatment.