MiR-21-5p in Macrophage-Derived Exosomes Targets Smad7 to Promote Epithelial Mesenchymal Transition of Airway Epithelial Cells

Abstract

Background: Asthma is usually associated with airway inflammation and airway remodeling. Epithelial mesenchymal transition (EMT) often occurs in airway remodeling. The purpose of this study is to identify the effect of miR-21-5p and Smad7 signaling pathway in macrophage-derived exosomes on EMT of airway epithelial cells. Methods: HE staining and Masson staining were used to verify the successful establishment of the asthma model. The levels of epithelial cell adhesion factor and stromal cell markers were detected by Western blot. The levels of miR-21-5p were detected by qRT-PCR. The expression of miR-21-5p in lung tissue was further verified by fluorescence in situ hybridization (FISH). Exosome morphology was observed by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Luciferase reporter assay was applied to analyze the interaction of miR-21-5p with Smad7. Results: The expression of miR-21-5p was upregulated in macrophages of rats in vivo with OVA-induced asthma. In vitro cultured alveolar macrophages stimulated by LPS could secrete exosomes with high levels of miR-21-5p. The exosome-derived miR-21-5p promotes EMT in rat tracheal epithelial cells through TGFβ1/Smad signaling pathway by downregulating Smad7. This process can be blocked by miR-21-5p inhibitor. Conclusion: Rat alveolar macrophages produced high levels of miR-21-5p-containing exosomes, which transported miR-21-5p to tracheal epithelial cells, thus promoting EMT through TGF-β1/Smad signaling pathway by targeting Smad7.

Macrophage-Related SPP1 as a Potential Biomarker for Early Lymph Node Metastasis in Lung Adenocarcinoma

“… Deng et al (2010) found that the abundant expression of tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) by macrophages can create a favorable inflammatory environment for the occurrence of colonic adenocarcinomas. Moreover, macrophages play a considerable role in the acquisition of the epithelial– mesenchymal transition (EMT) hallmarks observed in gastric cancer tissues ( Guan et al, 2021 ), pancreatic duct epithelial cells ( Otto et al, 2021 ), and tracheal epithelial cells ( Li et al, 2021 ), and EMT signatures plays a vital role in tumor metastasis ( Lu and Kang, 2019 ). Macrophages are heterogeneous cell clusters with intricate functions and forms.…”

MicroRNA‐21‐5p functions via RECK/MMP9 as a proalgesic regulator of the blood nerve barrier in nerve injury

“…As in silico analysis does not suggest a direct link between the two, we investigated possible pathways. miR‐21 regulates the TGF‐β signaling pathway by targeting mothers against decapentaplegic homolog 7 (SMAD7), ultimately leading to an increase in TGF‐β 35,36 . In mice, nerve Tgfb is increased after nerve injury 10 .…”

MiR-21 in Lung Transplant Recipients With Chronic Lung Allograft Dysfunction

“…MiR-21 was also strongly stained in alveolar macrophages, known source of TGF-β. Alveolar macrophages were found to produce high levels of miR-21 containing liposomes, which induced EMT in tracheal epithelial cells through TGF-β1/Smad signaling pathway (26). Therefore, it is reasonable to hypothesize that alveolar macrophages play a central role in promoting fibroproliferative mechanisms by secreting exosomes containing fibrosis inducers such as cytokines and miRNAs.…”