Di Stefano Antonino, Rosani Umberto, Levra Stefano, Gnemmi Isabella, Brun Paola, Maniscalco Mauro, D'Anna Silvestro Ennio, Carriero Vitina, Bertolini Francesca, Ricciardolo Fabio L M
Divisione di Pneumologia e Laboratorio di Citoimmunopatologia dell'Apparato Cardio Respiratorio, Istituti Clinici Scientifici Maugeri, IRCCS, 28010 Veruno, Italy.
Department of Biology, University of Padova, Via Ugo Bassi 58/b, 35121 Padova, Italy.
Biology (Basel). 2023 Oct 3;12(10):1304. doi: 10.3390/biology12101304.
Bone morphogenic proteins (BMPs) and their antagonists are involved in the tissue development and homeostasis of various organs.
To determine transcriptomic and protein expression of BMPs and their antagonists in stable COPD.
We measured the expression and localization of BMPs and some relevant antagonists in bronchial biopsies of stable mild/moderate COPD (MCOPD) (n = 18), severe/very severe COPD (SCOPD) (n = 16), control smokers (CS) (n = 13), and control non-smokers (CNS) (n = 11), and in lung parenchyma of MCOPD (n = 9), CS (n = 11), and CNS (n = 9) using immunohistochemistry and transcriptome analysis, in vitro after the stimulation of the 16HBE cells.
In bronchial biopsies, BMP4 antagonists CRIM1 and chordin were increased in the bronchial epithelium and lamina propria of COPD patients. BMP4 expression was decreased in the bronchial epithelium of SCOPD and MCOPD compared to CNS. Lung transcriptomic data showed non-significant changes between groups. CRIM1 and chordin were significantly decreased in the alveolar macrophages and alveolar septa in COPD patients. External 16HBE treatment with BMP4 protein reduced the bronchial epithelial cell proliferation.
These data show an imbalance between BMP proteins and their antagonists in the lungs of stable COPD. This imbalance may play a role in the remodeling of the airways, altering the regenerative-reparative responses of the diseased bronchioles and lung parenchyma.
骨形态发生蛋白（BMPs）及其拮抗剂参与多种器官的组织发育和内环境稳态。
确定稳定期慢性阻塞性肺疾病（COPD）中BMPs及其拮抗剂的转录组和蛋白表达情况。
我们使用免疫组织化学和转录组分析方法，检测了稳定期轻度/中度COPD（MCOPD）（n = 18）、重度/极重度COPD（SCOPD）（n = 16）、对照吸烟者（CS）（n = 13）和对照非吸烟者（CNS）（n = 11）支气管活检组织中BMPs及其一些相关拮抗剂的表达和定位，以及MCOPD（n = 9）、CS（n = 11）和CNS（n = 9）肺实质中BMPs及其一些相关拮抗剂的表达和定位，并在体外对16HBE细胞进行刺激后检测。
在支气管活检组织中，COPD患者支气管上皮和固有层中BMP4拮抗剂CRIM1和腱蛋白增加。与CNS相比，SCOPD和MCOPD支气管上皮中BMP4表达降低。肺转录组数据显示各组间无显著变化。COPD患者肺泡巨噬细胞和肺泡间隔中CRIM1和腱蛋白显著降低。用BMP4蛋白体外处理16HBE细胞可减少支气管上皮细胞增殖。
这些数据表明稳定期COPD患者肺中BMP蛋白与其拮抗剂之间存在失衡。这种失衡可能在气道重塑中起作用，改变患病细支气管和肺实质的再生修复反应。
