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揭示极化巨噬细胞衍生细胞外囊泡和 miRNA 特征对肺成纤维细胞中 TGF-β 调控的前沿影响。

Unveiling the Cutting-Edge Impact of Polarized Macrophage-Derived Extracellular Vesicles and MiRNA Signatures on TGF-β Regulation within Lung Fibroblasts.

机构信息

Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova and Padova City Hospital, 35128 Padova, Italy.

Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy.

出版信息

Int J Mol Sci. 2024 Jul 8;25(13):7490. doi: 10.3390/ijms25137490.

DOI:10.3390/ijms25137490
PMID:39000595
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11242851/
Abstract

Depending on local cues, macrophages can polarize into classically activated (M1) or alternatively activated (M2) phenotypes. This study investigates the impact of polarized macrophage-derived Extracellular Vesicles (EVs) (M1 and M2) and their cargo of miRNA-19a-3p and miRNA-425-5p on TGF-β production in lung fibroblasts. EVs were isolated from supernatants of M0, M1, and M2 macrophages and quantified using nanoscale flow cytometry prior to fibroblast stimulation. The concentration of TGF-β in fibroblast supernatants was measured using ELISA assays. The expression levels of miRNA-19a-3p and miRNA-425-5p were assessed via TaqMan-qPCR. TGF-β production after stimulation with M0-derived EVs and with M1-derived EVs increased significantly compared to untreated fibroblasts. miRNA-425-5p, but not miRNA-19a-3p, was significantly upregulated in M2-derived EVs compared to M0- and M1-derived EVs. This study demonstrates that EVs derived from both M0 and M1 polarized macrophages induce the production of TGF-β in fibroblasts, with potential regulation by miRNA-425-5p.

摘要

根据局部线索，巨噬细胞可以极化为经典激活型（M1）或替代激活型（M2）表型。本研究探讨了极化的巨噬细胞衍生的细胞外囊泡（EVs）（M1 和 M2）及其 miRNA-19a-3p 和 miRNA-425-5p 货物对肺成纤维细胞中 TGF-β产生的影响。使用纳米流式细胞术从 M0、M1 和 M2 巨噬细胞的上清液中分离 EVs，并在刺激成纤维细胞之前进行定量。使用 ELISA 测定法测量成纤维细胞上清液中 TGF-β的浓度。通过 TaqMan-qPCR 评估 miRNA-19a-3p 和 miRNA-425-5p 的表达水平。与未处理的成纤维细胞相比，用 M0 衍生的 EVs 和 M1 衍生的 EVs 刺激后 TGF-β的产生显著增加。与 M0 和 M1 衍生的 EVs 相比，M2 衍生的 EVs 中 miRNA-425-5p 而非 miRNA-19a-3p 的表达显著上调。这项研究表明，来自 M0 和 M1 极化巨噬细胞的 EVs 均可诱导成纤维细胞中 TGF-β的产生，其潜在的调节作用可能与 miRNA-425-5p 有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78bb/11242851/a6e5e379c833/ijms-25-07490-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78bb/11242851/999c0317fcd5/ijms-25-07490-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78bb/11242851/df7e01044859/ijms-25-07490-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78bb/11242851/53c80759190c/ijms-25-07490-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78bb/11242851/a6e5e379c833/ijms-25-07490-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78bb/11242851/999c0317fcd5/ijms-25-07490-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78bb/11242851/df7e01044859/ijms-25-07490-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78bb/11242851/53c80759190c/ijms-25-07490-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78bb/11242851/a6e5e379c833/ijms-25-07490-g004.jpg

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