LGMN促进肺纤维化中巨噬细胞和成纤维细胞之间的相互作用：一个潜在的治疗靶点
LGMN promotes crosstalk between macrophages and fibroblasts in pulmonary fibrosis: a potential therapeutic target.
摘要(中文译文)
巨噬细胞在特发性肺纤维化（IPF）的进展中发挥关键作用。本研究旨在鉴定基于巨噬细胞相关基因的预测特征，以预测患者预后并发现IPF的潜在治疗靶点。我们分析了来自GEO数据库的单细胞转录组和微阵列数据，探索健康对照、COPD和IPF患者中的细胞变异。分别利用CellChat和Monocle分析细胞相互作用和拟时序轨迹。采用生物信息学方法鉴定差异表达基因，并通过多因素Cox回归开发基因特征，利用ROC曲线和外部数据集进行验证。通过体内外实验研究LGMN的生物学功能。我们观察到IPF患者中单核细胞来源巨噬细胞（MDMs）显著增加，且与肺功能呈负相关。在IPF患者中，巨噬细胞与成纤维细胞以及肌成纤维细胞之间的相互作用较对照组更为频繁和强烈。值得注意的是，TGF-β1信号通路在IPF中显著激活，尤其是在MDMs和肌成纤维细胞中，导致细胞外基质（ECM）活性增加。我们开发了一个与MDMs相关的基因特征，可作为IPF患者的独立预后工具。实验证明M2巨噬细胞中LGMN水平升高，并与纤维化肺组织中的CD206共定位。使用LGMN抑制剂RR-11a处理可减少M2巨噬细胞分泌TGF-β1，从而减弱巨噬细胞与成纤维细胞之间的通讯，并减轻博来霉素诱导的小鼠肺纤维化。我们的研究建立了一个与MDMs相关的基因特征，可能有助于临床医生对IPF进行个性化管理。此外，我们确定LGMN是M2巨噬细胞与成纤维细胞相互作用的促进因子，提示其作为IPF治疗靶点的潜力。
Abstract
Macrophages play a crucial role in the progression of idiopathic pulmonary fibrosis (IPF). This study aims to identify a predictive signature based on macrophage-related genes to forecast patient prognosis and uncover potential therapeutic targets for IPF. We analyzed single-cell transcriptomic and microarray data from the GEO database, exploring cellular variations in healthy controls, COPD, and IPF patients. CellChat and Monocle were utilized for analyzing cell interactions and pseudotime trajectories, respectively. Bioinformatics was used to identify differentially expressed genes, leading to the development of a gene signature via multivariate Cox regression, which was validated using ROC curves and an external dataset. The biological function of LGMN was investigated through and experiments. We observed a significant increase in monocyte-derived macrophages (MDMs) in patients with IPF, which negatively correlated with lung function. In IPF patients, interactions between macrophages and fibroblasts, as well as myofibroblasts, were both more frequent and intense compared to those observed in controls. Notably, the TGF-β1 signaling pathway was significantly activated in IPF, particularly within MDMs and myofibroblasts, leading to increased extracellular matrix (ECM) activity. We developed a gene signature associated with MDMs, which serves as an independent prognostic tool for IPF patients. experiments demonstrated elevated levels of LGMN in M2 macrophages, co-localizing with CD206 in fibrotic lung tissue. Treatment with RR-11a, a LGMN inhibitor, reduced TGF-β1 secretion from M2 macrophages, thereby diminishing communication between macrophages and fibroblasts and alleviating bleomycin-induced pulmonary fibrosis in mice. Our research establishes a gene signature associated with MDMs, which may aid clinicians in the personalized management of IPF. Additionally, we identify LGMN as a promoter of interaction between M2 macrophages and fibroblasts, suggesting its potential as a therapeutic target for IPF treatment.
如何引用
AMA
Yuechong Xia, Fang Zhou, Boyue Ma, Haixia Gong, Mengyang Jing, Liping Dai, et al. LGMN promotes crosstalk between macrophages and fibroblasts in pulmonary fibrosis: a potential therapeutic target.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1789907.
APA
Yuechong Xia, Fang Zhou, Boyue Ma, Haixia Gong, Mengyang Jing, Liping Dai, et al (2026). LGMN promotes crosstalk between macrophages and fibroblasts in pulmonary fibrosis: a potential therapeutic target.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1789907
GB/T 7714
Yuechong Xia, Fang Zhou, Boyue Ma, Haixia Gong, Mengyang Jing, Liping Dai, et al. LGMN promotes crosstalk between macrophages and fibroblasts in pulmonary fibrosis: a potential therapeutic target.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1789907.
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