Chronic obstructive pulmonary disease (COPD), characterized by chronic inflammation, is a recognized global health crisis. Sialic acid-binding immunoglobulin-like lectin 1 (siglec1 or CD169), mainly expressed in macrophages and dendritic cells, is markedly upregulated after encountering pathogens or under acute/chronic inflammation conditions. However, it is rarely reported that whether siglec1 plays a role in the development of COPD. In this study, we found that siglec1 had higher expression in the lungs from COPD rats and in peripheral blood mononuclear cells (PBMCs) from COPD patients. Knockdown of siglec1 in vivo and in vitro dramatically decreased pro-inflammatory cytokines production in pulmonary macrophages and alleviated pulmonary inflammatory responses in COPD rats as well as inactivated nuclear factor kappa B (NF-κB) signaling. In addition, we identified a new microRNA, miR-195-5p, which has never explored in COPD, was lower expressed in COPD rats and PBMC of COPD patients, and could negatively modulate siglec1 expression in macrophages. Moreover, overexpression of miR-195-5p via miR-195-5p mimics in vitro and in vivo could significantly alleviate pro-inflammatory cytokines production in pulmonary macrophages and pulmonary inflammatory responses in COPD rats. Together, our findings suggested that miR-195-5p inhibited the development of COPD via targeting siglec1, which might become a therapeutic target to improve COPD.

中文翻译：

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MiR-195-5p通过靶向siglec1抑制慢性阻塞性肺疾病的发展。

慢性阻塞性肺疾病（COPD）以慢性炎症为特征，是公认的全球性健康危机。唾液酸结合免疫球蛋白样凝集素1（siglec1或CD169）主要在巨噬细胞和树突状细胞中表达，在遇到病原体或在急性/慢性炎症条件下会明显上调。但是，很少有人报道siglec1是否在COPD的发生中起作用。在这项研究中，我们发现siglec1在COPD大鼠的肺部和COPD患者的外周血单核细胞（PBMC）中具有较高的表达。体内和体外抑制siglec1可显着降低肺巨噬细胞中促炎细胞因子的产生，并减轻COPD大鼠的肺炎性反应以及灭活的核因子κB（NF-κB）信号传导。此外，我们发现了一种新的microRNA，miR-195-5p，从未在COPD中进行探索，在COPD大鼠和COPD患者的PBMC中表达较低，并且可能对巨噬细胞中的siglec1表达产生负调控。此外，在体外和体内通过miR-195-5p模拟物表达miR-195-5p可以显着减轻肺巨噬细胞中促炎性细胞因子的产生和COPD大鼠的肺炎性反应。在一起，我们的发现表明，miR-195-5p通过靶向siglec1抑制了COPD的发展，而siglec1可能成为改善COPD的治疗靶标。在体外和体内通过miR-195-5p模拟物过度表达miR-195-5p可以显着减轻COPD大鼠肺巨噬细胞中促炎性细胞因子的产生和肺部炎症反应。在一起，我们的发现表明，miR-195-5p通过靶向siglec1抑制了COPD的发展，而siglec1可能成为改善COPD的治疗靶标。在体外和体内通过miR-195-5p模拟物过度表达miR-195-5p可以显着减轻COPD大鼠肺巨噬细胞促炎细胞因子的产生和肺部炎症反应。在一起，我们的发现表明，miR-195-5p通过靶向siglec1抑制了COPD的发展，而siglec1可能成为改善COPD的治疗靶标。