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Transcriptomic Analysis Reveals a Link Between Hippo Signaling Pathway and Macrophages in Lungs of Mice with
Huan Xiao1, Qian-Nan Zhang1, Qi-Xiang Sun2
1Department of Emergency, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, People's Republic of China.
Purpose:
The Hippo signaling pathway participates in the restriction of cell proliferation and organ growth. Activated macrophages have been implicated in the pathogenesis of allergic asthma. Recent studies have shown that Hippo signaling pathway may also be involved in the regulation of asthma. However, the link between Hippo signaling pathway and macrophages in the context of allergic asthma has not been investigated. The purpose of this study was to explore the link between Hippo signaling pathway and macrophages using a mice model of OVA-induced allergic asthma.
Methods:
Mice models of asthma were established. Lung tissues were collected from mice and pooled for mRNA sequencing and bioinformatics analysis. The relative mRNA expression of Hippo signalling pathway-related proteins Yap1, Lef1 and Ctgf was also measured. Double immunofluorescence staining was performed on lung tissues to evaluate macrophage marker F4/80 expression and Yap1/Lef1/Ctgf expression.
Results:
Results of the RNA-Seq of lung tissues demonstrated that the Hippo signaling pathway was down-regulated in OVA-induced allergic asthma. Using the cytoHubba tool kits in Cytoscape, the following top 10 hub genes of Hippo signalling pathway were identified: Yap1, Lef1, Ctgf, Ccnd1, Axin2, Smad7, Wnt4, Wnt3a, Pard6b, and Wwc1. Using the seq-ImmuCC (http://218.4.234.74:3200/immune/), a negative correlation was found between macrophages and Hippo signaling pathway activity (R2 = 0.93). The mRNA expression levels of pulmonary Yap1, Lef1, and Ctgf were down-regulated in the mice model of OVA-induced allergic asthma. Moreover, double-stained immunofluorescence for F4/80 and Yap1, Lef1, Ctgf in mouse lung sections respectively revealed that macrophage proliferation was correlated with downregulation of the Hippo signaling pathway in the mice model of OVA-induced allergic asthma.
Conclusion:
These results demonstrated that the Hippo signaling pathway was down-regulated in asthma mice, and the proliferation of macrophages was associated with downregulation of the Hippo signaling pathway. These findings reveal novel insights into the pathogenesis and treatment of asthma.
Insights
The Hippo signaling pathway is down-regulated in asthma, correlating with increased macrophage proliferation. This suggests a novel link between the Hippo pathway and allergic asthma pathogenesis.
Area of Science:
- Cell Biology
- Immunology
- Respiratory Medicine
Background:
- The Hippo signaling pathway regulates cell proliferation and organ size.
- Activated macrophages are key players in allergic asthma pathogenesis.
- Emerging evidence suggests the Hippo pathway's involvement in asthma regulation.
Purpose of the Study:
- To investigate the relationship between the Hippo signaling pathway and macrophages in a mouse model of allergic asthma.
- To explore the potential role of Hippo signaling in asthma pathogenesis.
Main Methods:
- Established a mouse model of ovalbumin (OVA)-induced allergic asthma.
- Performed RNA sequencing and bioinformatics analysis on lung tissues.
- Quantified mRNA expression of Hippo pathway components (Yap1, Lef1, Ctgf).
- Utilized double immunofluorescence staining to assess macrophage (F4/80) and Hippo pathway protein expression.
Main Results:
- Hippo signaling pathway was significantly down-regulated in OVA-induced allergic asthma.
- Identified Yap1, Lef1, and Ctgf as key down-regulated genes within the pathway.
- Found a strong negative correlation between macrophage activity and Hippo signaling pathway activity (R² = 0.93).
- Demonstrated that macrophage proliferation in asthma models is associated with Hippo signaling pathway downregulation.
Conclusions:
- The Hippo signaling pathway is downregulated in allergic asthma.
- Macrophage proliferation in asthma is linked to the downregulation of the Hippo signaling pathway.
- These findings offer new perspectives on asthma pathogenesis and potential therapeutic strategies.
