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抑制DLL4/Notch信号通路可促进肺动脉高压中的M2极化和细胞增殖。

Inhibition of DLL4/Notch Signaling Pathway Promotes M2 Polarization and Cell Proliferation in Pulmonary Arterial Hypertension.

作者信息

Tan Guangxing, Juan Chenxia, Mao Yan, Xue Gang, Fang Zhuyuan

机构信息

Institute of Hypertension, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, China.

Wuxi Hospital of Traditional Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Wuxi, Jiangsu 214045, China.

出版信息

ACS Omega. 2024 Aug 26;9(36):37923-37933. doi: 10.1021/acsomega.4c04307. eCollection 2024 Sep 10.

DOI:10.1021/acsomega.4c04307
PMID:39281910
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11391436/
Abstract

In this study, we conducted a comprehensive analysis to identify key genes and pathways associated with pulmonary arterial hypertension (PAH) and investigated the role of delta-like ligand 4 (DLL4) in PAH pathogenesis. Through integrated analysis of multiple data sets, we identified 6 candidate differentially expressed genes (DEGs), notably , which showed the highest distinguishing efficiency between PAH and control samples. Functional and pathway enrichment analyses revealed the involvement of in critical biological processes and pathways related to PAH, including notch signaling, immune cell function, and inflammatory responses. Further investigation demonstrated that decreased expression correlated with increased M2 macrophage polarization, suggesting a potential role for in preventing M2 differentiation. Additionally, the DLL4/Notch1 axis was found to influence the Notch profile and regulate signaling mediators during M2 differentiation. These findings highlight as a promising biomarker and therapeutic target for PAH, shedding light on the underlying molecular mechanisms and providing insights for the development of novel treatment strategies.

摘要

在本研究中，我们进行了全面分析以鉴定与肺动脉高压（PAH）相关的关键基因和通路，并研究了Delta样配体4（DLL4）在PAH发病机制中的作用。通过对多个数据集的综合分析，我们鉴定出6个候选差异表达基因（DEG），其中[基因名称未给出]在PAH和对照样本之间显示出最高的区分效率。功能和通路富集分析揭示了[基因名称未给出]参与了与PAH相关的关键生物学过程和通路，包括Notch信号传导、免疫细胞功能和炎症反应。进一步研究表明，[基因名称未给出]表达降低与M2巨噬细胞极化增加相关，提示[基因名称未给出]在预防M2分化中具有潜在作用。此外，发现DLL4/Notch1轴在M2分化过程中影响Notch谱并调节信号传导介质。这些发现突出了[基因名称未给出]作为PAH有前景的生物标志物和治疗靶点，揭示了潜在的分子机制，并为新型治疗策略的开发提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddcc/11391436/1e39c88685bd/ao4c04307_0009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddcc/11391436/1e39c88685bd/ao4c04307_0009.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddcc/11391436/c438b240fe16/ao4c04307_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddcc/11391436/932b39817a12/ao4c04307_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddcc/11391436/84d283a5535a/ao4c04307_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddcc/11391436/34d2593846a4/ao4c04307_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddcc/11391436/a7f29fbc5ec1/ao4c04307_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddcc/11391436/97cd283205cd/ao4c04307_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddcc/11391436/d8a86a1bd288/ao4c04307_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ddcc/11391436/1e39c88685bd/ao4c04307_0009.jpg

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Single-Cell Imaging Maps Inflammatory Cell Subsets to Pulmonary Arterial Hypertension Vasculopathy.
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Am J Respir Crit Care Med. 2024 Jan 15;209(2):206-218. doi: 10.1164/rccm.202209-1761OC.
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