Scholarlink

<p>Circular RNAs (circRNAs) have emerged as key regulators in human diseases, yet their mechanisms of action in chronic obstructive pulmonary disease (COPD) remain largely unknown. In this study, the conserved mammalian circRNA circFCHO2 was shown to play critical roles in COPD. The expression level of circFCHO2 was significantly increased in COPD cell models, mouse models, and human lung tissue samples. Moreover, we demonstrated that circFCHO2 promotes epithelial‒mesenchymal transition (EMT) in bronchial epithelial cells and extracellular matrix (ECM) remodeling. Mechanistically, circFCHO2 binds to and facilitates the nuclear translocation of PTBP1, thereby inhibiting the splicing of GRN pre-mRNA, which reduces PGRN protein expression levels and activates the NF-κB pathway. This activation of the NF-κB signaling pathway regulates the expression of EMT and ECM remodeling-related proteins, leading to the occurrence of airway remodeling. circFCHO2 knockdown reverses cigarette smoke-induced emphysema and airway remodeling of COPD in mice. Overall, our study advanced the understanding of the molecular mechanisms by which circRNAs contribute to airway remodeling in COPD patients.</p><p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Circular RNA FCHO2 promotes airway remodeling in COPD via regulating nuclear translocation of PTBP1 to repress the splicing of GRN pre-mRNA

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月3日

查看全文
  • Yanfei Liu,
  • Yucong Wang,
  • Yuqing Fei,
  • Hu Xu,
  • Cheng Xue,
  • Liudong Li,
  • Lei Huang,
  • Pengcheng Liu,
  • Renming Li,
  • Ge Shan,
  • Liang Chen,
  • Dahai Zhao

摘要

Circular RNAs (circRNAs) have emerged as key regulators in human diseases, yet their mechanisms of action in chronic obstructive pulmonary disease (COPD) remain largely unknown. In this study, the conserved mammalian circRNA circFCHO2 was shown to play critical roles in COPD. The expression level of circFCHO2 was significantly increased in COPD cell models, mouse models, and human lung tissue samples. Moreover, we demonstrated that circFCHO2 promotes epithelial‒mesenchymal transition (EMT) in bronchial epithelial cells and extracellular matrix (ECM) remodeling. Mechanistically, circFCHO2 binds to and facilitates the nuclear translocation of PTBP1, thereby inhibiting the splicing of GRN pre-mRNA, which reduces PGRN protein expression levels and activates the NF-κB pathway. This activation of the NF-κB signaling pathway regulates the expression of EMT and ECM remodeling-related proteins, leading to the occurrence of airway remodeling. circFCHO2 knockdown reverses cigarette smoke-induced emphysema and airway remodeling of COPD in mice. Overall, our study advanced the understanding of the molecular mechanisms by which circRNAs contribute to airway remodeling in COPD patients.