Knockdown of SOX9 alleviates tracheal fibrosis through the Wnt/beta-catenin signaling pathway

作者全名："Gu, Lei; Li, Anmao; Lin, Jing; Gan, Yiling; He, Chunyan; Xiao, Rui; Liao, Jiaxin; Li, Yishi; Guo, Shuliang"

作者地址："[Gu, Lei; Li, Anmao; Gan, Yiling; He, Chunyan; Xiao, Rui; Liao, Jiaxin; Li, Yishi; Guo, Shuliang] Chongqing Med Univ, Affiliated Hosp 1, Dept Resp & Crit Care Med, Chongqing, Peoples R China; [Lin, Jing] Wenzhou Med Univ, Affiliated Hosp 1, Dept Infect Dis, Wenzhou, Peoples R China"

通信作者："Li, YS; Guo, SL (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Resp & Crit Care Med, Chongqing, Peoples R China."

来源：JOURNAL OF MOLECULAR MEDICINE-JMM

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000865223400001

JCR分区：Q2

影响因子：4.7

年份：2022

卷号：100

期号：11

开始页：1659

结束页：1670

文献类型：Article

关键词：SOX9; Tracheal fibrosis; Granulation tissue hyperplasia; ECM; Wnt/beta-catenin pathway

摘要："Trachealfibrosis is an important cause of tracheal stenosis without effective treatments, and new drug targets need to be developed. The role of SOX9 in the injury and repair of the trachea is unknown; this study aims to investigate the role of SOX9 in the regulation of tracheal fibrosis based on clinical samples from patients with tracheal injury and a model of tracheal fibrosis produced by tracheal brushing in rats. The results showed that the expressions of SOX9 and mesenchymal and ECM-related indicators were increased in the injury and fibrosis of the trachea in patients and rats. Serum SOX9 levels exhibited a sensitivity of 83.87% and specificity of 90% in distinguishing patients with tracheal fibrosis from healthy volunteers when the cut-off value was 13.24 ng/ml. Knockdown SOX9 can markedly inhibit granulation tissue proliferation, reduce inflammation and ECM deposition, promote epithelial regeneration and granulation tissue apoptosis, and attenuate the tracheal fibrosis after injury. Additionally, RNA sequencing showed that the proliferation, migration, and ECM deposition of tracheal granulation tissue were related to the activation of Wnt pathway, activation of the beta-catenin, and p-GSK3 beta after injury can be inhibited by the knockdown of SOX9. In summary, SOX9 is upregulated in tracheas fibrosis and may be a novel factor to promote tracheal fibrosis progression. Inhibiting SOX9 may be used to prevent and treat tracheal fibrosis in the future."

基金机构："National Major Science and Technology Projects of China [2018ZX10302302003]; Chongqing talents projects-Famous masters and teachers; Chongqing young and middle-aged medical high-end talent studio-Lung Nodule Studio; Postgraduate Research and Innovation Project of Chongqing, China [CYB21173]"

基金资助正文："This study was supported by the National Major Science and Technology Projects of China (grant number 2018ZX10302302003) and Chongqing talents projects-Famous masters and teachers (Shuliang Guo) and Chongqing young and middle-aged medical high-end talent studio-Lung Nodule Studio and the Postgraduate Research and Innovation Project of Chongqing, China (CYB21173)."