SPP1-mediated crosstalk between macrophage and fibroblasts promotes benign airway stenosis
1The First Department of Pulmonary and Critical Care Medicine, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Respiratory Critical Care Medicine, Hebei Institute of Respiratory Diseases, Shijiazhuang, 050000, Hebei Province, China.
Objective:
The aim of this study is to elucidate the role of M2 macrophages in the pathogenesis of benign airway stenosis using a Sprague Dawley (SD) rat model and in vitro macrophage-fibroblast co-culture systems.
Methods:
Ligand-receptor interactions mediating cellular crosstalk between macrophages and fibroblasts were identified through single-cell RNA sequencing-based bioinformatics analysis. An airway stenosis model was established in SD rats, which were assigned to five experimental groups: normal control and post-modeling days 1 (D1), 4 (D4), 7 (D7), and 14 (D14). Temporal changes in M2 macrophage infiltration and their involvement in airway remodeling were assessed. Fibroblasts isolated from human granulation tissue and normal airway tissue were evaluated for differential activation of intracellular signaling pathways. In vitro macrophage-fibroblast co-culture systems involving M2 macrophages and fibroblasts were conducted to assess molecular signaling interactions.
Results:
A progressive increase in M2 macrophage infiltration was observed during the development of airway stenosis, accompanied by upregulation of secreted phosphoprotein-1 (SPP1) and activation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway. Fibroblasts derived from granulation tissue exhibited higher levels of pathway activation compared to normal fibroblasts.In co-culture, M2 macrophages induced fibroblast activation and fibrogenesis via SPP1-mediated signaling. Administration of rapamycin, an mTOR pathway inhibitor, significantly reduced granulation tissue formation and improved airway patency in the rat model.
Conclusion:
M2 macrophages contribute to fibrotic airway remodeling in benign airway stenosis through SPP1-mediated activation of the PI3K/AKT/mTOR signaling pathway in fibroblasts. Pharmacological targeting of this axis with rapamycin may represent a potential therapeutic strategy for mitigating fibrosis in benign airway stenosis.
Insights
M2 macrophages drive airway stenosis fibrosis by activating fibroblast signaling. Inhibiting this pathway with rapamycin shows therapeutic potential for benign airway stenosis.
Area of Science:
- Immunology
- Cell Biology
- Pulmonology
Background:
- Benign airway stenosis involves complex cellular interactions.
- Understanding the role of immune cells like macrophages is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of M2 macrophages in benign airway stenosis pathogenesis.
- To explore the molecular mechanisms of macrophage-fibroblast crosstalk in airway remodeling.
- To evaluate rapamycin as a potential therapeutic agent.
Main Methods:
- Utilized a Sprague Dawley rat model of airway stenosis.
- Employed single-cell RNA sequencing for bioinformatics analysis of ligand-receptor interactions.
- Conducted in vitro co-culture systems of M2 macrophages and fibroblasts.
- Assessed M2 macrophage infiltration and airway remodeling markers.
Main Results:
- Increased M2 macrophage infiltration correlated with airway stenosis progression.
- M2 macrophages induced fibroblast activation and fibrogenesis via secreted phosphoprotein-1 (SPP1) signaling.
- Activation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway was observed.
- Rapamycin treatment reduced granulation tissue and improved airway patency in rats.
Conclusions:
- M2 macrophages promote fibrotic airway remodeling in benign airway stenosis via SPP1-mediated PI3K/AKT/mTOR activation in fibroblasts.
- Targeting the SPP1-PI3K/AKT/mTOR axis with rapamycin offers a potential therapeutic strategy.
More Related Videos
Related Concept Videos
01:20Chronic Obstructive Pulmonary Disease-II: Pathophysiology
Chronic Inflammation
01:26Asthma-II: Pathophysiology and Classification
Additionally, environmental and genetic factors play crucial roles in determining an individual's susceptibility to asthma and the severity of their condition.
Critical processes in asthma pathophysiology include:
01:20Asthma: Pathogenesis and Management
Asthma is classified as allergic and non-allergic. Allergens such as dust mites, pollen, and pet dander trigger allergic asthma, while factors like cold air, intense emotions, or exercise can induce non-allergic asthma.
01:16TGF - β Signaling Pathway
01:24Regulation of Angiogenesis and Blood Supply