Macrophage‐derived exosomes mediate silica‐induced pulmonary fibrosis by activating fibroblast in an endoplasmic reticulum stress‐dependent manner

Qin, Xiaofeng; Lin, Xin; Liu, Ying; Li, Xiang; Deng, Zhili; Chen, Huiping; Chen, Hui; Niu, Zhiyuan; Li, Zisheng; Hu, Yongbin

doi:10.1111/jcmm.16524

Cited by 34 publications

(36 citation statements)

References 52 publications

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“…EVs have been isolated from silica-exposed Mφ and found to induce the proliferation of myofibroblasts and fibroblasts and increase their expression levels of SPP1 ( 36 ). They also induce the overproduction of proinflammatory cytokines and promote myofibroblast activation in an endoplasmic reticulum stress-dependent manner ( 30 ).…”

Section: Immunomodulatory Effects Of Mφ-evs In Chronic Inflammatory Diseasementioning

confidence: 99%

The Immuno-Modulation Effect of Macrophage-Derived Extracellular Vesicles in Chronic Inflammatory Diseases

et al. 2021

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As natural nanocarriers and intercellular messengers, extracellular vesicles (EVs) control communication among cells. Under physiological and pathological conditions, EVs deliver generic information including proteins and nucleic acids to recipient cells and exert regulatory effects. Macrophages help mediate immune responses, and macrophage-derived EVs may play immunomodulatory roles in the progression of chronic inflammatory diseases. Furthermore, EVs derived from various macrophage phenotypes have different biological functions. In this review, we describe the pathophysiological significance of macrophage-derived extracellular vesicles in the development of chronic inflammatory diseases, including diabetes, cancer, cardiovascular disease, pulmonary disease, and gastrointestinal disease, and the potential applications of these EVs.

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Section: Immunomodulatory Effects Of Mφ-evs In Chronic Inflammatory Diseasementioning

confidence: 99%

The Immuno-Modulation Effect of Macrophage-Derived Extracellular Vesicles in Chronic Inflammatory Diseases

et al. 2021

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“…PFD has proven its anti-inflammatory, antioxidant, and anti-fibrotic effects in many fibrotic diseases. Since PFD reduced the severity of silicosis by inhibiting the epithelial mesenchymal transition (EMT), regulating the TGF-β 1/Smad2/3 signaling pathway ( Wang et al, 2020 ; Qin et al, 2021 ), and inhibiting the production of IL-17A (24), we used it as a positive control in our study. AKEX0011 is not inferior to PFD in the prevention and treatment of silicosis.…”

Section: Discussionmentioning

confidence: 99%

“…Although there is no M2 polarization under silica stimulation in vitro , various in vitro experiments have shown that silica can facilitate the secretion of pro-fibrotic factors in macrophages to aggravate pulmonary fibrosis ( Pang et al, 2021 ). Silica-exposed macrophage-derived exosomes can activate fibroblasts to proliferate and to express collagen I and α-SMA ( Wang et al, 2020 ; Qin et al, 2021 ). Our experiments also proved that silica can induce macrophages secreting TGF-β, and AKEX0011 can alleviate this effect.…”

Section: Discussionmentioning

confidence: 99%

A Novel N-Arylpyridone Compound Alleviates the Inflammatory and Fibrotic Reaction of Silicosis by Inhibiting the ASK1-p38 Pathway and Regulating Macrophage Polarization

et al. 2022

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Silicosis is one of the potentially fatal occupational diseases characterized by respiratory dysfunction, chronic interstitial inflammation, and fibrosis, for which treatment options are limited. Previous studies showed that a novel N-arylpyridone compound named AKEX0011 exhibited anti-inflammatory and anti-fibrotic effects in bleomycin-induced pulmonary fibrosis; however, it is unknown whether it could also be effective against silicosis. Therefore, we sought to investigate the preventive and therapeutic roles of AKEX0011 in a silicosis rodent model and in a silica-stimulated macrophage cell line. In vivo, our results showed that AKEX0011 ameliorated silica-induced imaging lung damages, respiratory dysfunction, reduced the secretion of inflammatory and fibrotic factors (TNF-α, IL-1β, IL-6, TGF-β, IL-4, and IL-10), and the deposition of fibrosis-related proteins (collagen I, fibronectin, and α-SMA), regardless of early or advanced therapy. Specifically, we found that AKEX0011 attenuated silicosis by inhibiting apoptosis, blocking the ASK1-p38 MAPK signaling pathway, and regulating polarization of macrophages. In vitro, AKEX0011 inhibited macrophages from secreting inflammatory cytokines and inhibited apoptosis of macrophages in pre-treated and post-treated models, concurrent with blocking the ASK1-p38 pathway and inhibiting M1 polarization. Collectively, AKEX0011, as a novel N-arylpyridone compound, exerted protective effects for silica-induced pulmonary inflammation and fibrosis both in vivo and in vitro, and hence, it could be a strong drug candidate for the treatment of silicosis.

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“…Recently, it has been demonstrated that EVs secretion increases in the supernatant of silica (SiO 2 )-stimulated macrophage. Moreover, lung fibroblasts incubated with these EVs are differentiated into myofibroblasts by inducing endoplasmic reticulum stress, which results in a significant increase in proliferation, migration, and expression of fibrotic proteins, such as collagen I and α-SMA [ 57 ]. Besides, recently, it was reported that miR-125a-5p is upregulated in EVs of silica (SiO 2 )-stimulated macrophage, and when lung fibroblasts are incubated with these EVs, α-SMA is overexpressed, and TGF-β is activated to mediate their differentiation into myofibroblasts through downregulation of Smurf1 [ 58 ].…”

Section: Evs and Their Involvement In Cellular And Molecular Mechanis...mentioning

confidence: 99%

The Role of Extracellular Vesicles in Idiopathic Pulmonary Fibrosis Progression: An Approach on Their Therapeutics Potential

Ramírez-Hernández

Velázquez-Enríquez

Santos-Álvarez

et al. 2022

Cells

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Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease of unknown etiology. Different types of cells are involved in fibrogenesis, which is persistently physical and molecular stimulation, either directly or by interacting with bioactive molecules and extracellular vesicles (EVs). Current evidence suggests that EVs play an essential role in IPF development. EVs are released by a variety of cells, including fibroblasts, epithelial cells, and alveolar macrophages. In addition, EVs can transport bioactive molecules, such as lipids, proteins, and nucleic acids, which play a pivotal role in cellular communication. Several proposed mechanisms show that an acceptor cell can capture, absorb, or interact with EVs through direct fusion with the plasma membrane, ligand–receptor interaction, and endocytotic process, modifying the target cell. During fibrogenesis, the release of EVs is deregulated, increases the EVs amount, and the cargo content is modified. This alteration is closely associated with the maintenance of the fibrotic microenvironment. This review summarizes the current data on the participation of EVs secreted by the cells playing a critical role in IPF pathogenesis.

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Macrophage‐derived exosomes mediate silica‐induced pulmonary fibrosis by activating fibroblast in an endoplasmic reticulum stress‐dependent manner

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 34 publications

References 52 publications

The Immuno-Modulation Effect of Macrophage-Derived Extracellular Vesicles in Chronic Inflammatory Diseases

The Immuno-Modulation Effect of Macrophage-Derived Extracellular Vesicles in Chronic Inflammatory Diseases

A Novel N-Arylpyridone Compound Alleviates the Inflammatory and Fibrotic Reaction of Silicosis by Inhibiting the ASK1-p38 Pathway and Regulating Macrophage Polarization

The Role of Extracellular Vesicles in Idiopathic Pulmonary Fibrosis Progression: An Approach on Their Therapeutics Potential

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