Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, No.180 Fenglin Road, Shanghai, 200032, China.
Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Respir Res. 2022 Oct 1;23(1):269. doi: 10.1186/s12931-022-02193-5.
The defects and imbalance in lung repair and structural maintenance contribute to the pathogenesis of chronic obstructive pulmonary diseases (COPD), yet the molecular mechanisms that regulate lung repair process are so far incompletely understood. We hypothesized that cigarette smoking causes glycocalyx impairment and endothelial apoptosis in COPD, which could be repaired by the stimulation of fibroblast growth factor 10 (FGF10)/FGF receptor 1 (FGFR1) signaling.
We used immunostaining (immunohistochemical [IHC] and immunofluorescence [IF]) and enzyme-linked immunosorbent assay (ELISA) to detect the levels of glycocalyx components and endothelial apoptosis in animal models and in patients with COPD. We used the murine emphysema model and in vitro studies to determine the protective and reparative role of FGF10/FGFR1.
Exposure to cigarette smoke caused endothelial glycocalyx impairment and emphysematous changes in murine models and human specimens. Pretreatment of FGF10 attenuated the development of emphysema and the shedding of glycocalyx components induced by CSE in vivo. However, FGF10 did not attenuate the emphysema induced by endothelial-specific killing peptide CGSPGWVRC-GG-(KLAKLAK). Mechanistically, FGF10 alleviated smoke-induced endothelial apoptosis and glycocalyx repair through FGFR1/ERK/SOX9/HS6ST1 signaling in vitro. FGF10 was shown to repair pulmonary glycocalyx injury and endothelial apoptosis, and attenuate smoke-induced COPD through FGFR1 signaling.
Our results suggest that FGF10 may serve as a potential therapeutic strategy against COPD via endothelial repair and glycocalyx reconstitution.
肺部修复和结构维持的缺陷和失衡导致慢性阻塞性肺疾病（COPD）的发病机制，但调节肺部修复过程的分子机制至今仍不完全了解。我们假设吸烟导致 COPD 中糖萼损伤和内皮细胞凋亡，而纤维母细胞生长因子 10（FGF10）/成纤维细胞生长因子受体 1（FGFR1）信号刺激可修复这些损伤。
我们使用免疫染色（免疫组织化学[IHC]和免疫荧光[IF]）和酶联免疫吸附试验（ELISA）检测动物模型和 COPD 患者中糖萼成分和内皮细胞凋亡的水平。我们使用小鼠肺气肿模型和体外研究来确定 FGF10/FGFR1 的保护和修复作用。
香烟暴露导致小鼠模型和人体标本中的内皮糖萼损伤和肺气肿。FGF10 预处理可减轻 CSE 诱导的肺气肿和糖萼成分脱落。然而，FGF10 并不能减轻内皮特异性杀伤肽 CGSPGWVRC-GG-(KLAKLAK)诱导的肺气肿。在机制上，FGF10 通过体外 FGFR1/ERK/SOX9/HS6ST1 信号减轻烟雾诱导的内皮细胞凋亡和糖萼修复。FGF10 通过 FGFR1 信号修复肺糖萼损伤和内皮细胞凋亡，并减轻烟雾引起的 COPD。
我们的结果表明，FGF10 可能通过内皮修复和糖萼重建成为治疗 COPD 的潜在治疗策略。
