Extracellular Vesicles from Fibroblasts Induce Epithelial-Cell Senescence in Pulmonary Fibrosis

Kadota, Tsukasa; Yoshioka, Yusuke; Fujita, Yu; Araya, Jun; Minagawa, Shunsuke; Hara, Hiromichi; Miyamoto, Atsushi; Suzuki, Souichiro; Fujimori, Sakashi; Kohno, Tadasu; Fujii, Takeshi; Kishi, Kazuma; Kuwano, Kazuyoshi; Ochiya, Takahiro

doi:10.1165/rcmb.2020-0002oc

Cited by 79 publications

(70 citation statements)

References 50 publications

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“…Although the development and internal validation cohort in this study were small, it provides a foundation for future work in a larger cohort. The second study evaluating lung fibroblast-derived EVs revealed similar findings; IPF lung fibroblast-derived EVs were enriched in miR-23b-3p and miR-494-3p, which correlated with disease severity [ 80 ]. Together, microRNA-associated EVs derived from sputum, BALF, and circulation can potentially be used as diagnostic and prognostic markers for ILD.…”

Section: Extracellular Vesicles As Biomarkersmentioning

confidence: 91%

“…The involvement of EVs in other chronic lung diseases such as COPD and lung cancer through cellular senescence was reviewed previously [ 79 ]. In ILD, one study showed that IPF fibroblast EV-associated miR-23b-3p and miR-494-3p induced human bronchial epithelial cells= senescence by suppressing SIRT3 expression, mitochondrial damage in epithelial cells, and senescence [ 80 ]. We have shown that EVs from human IPF lungs and bleomycin-injured mouse lungs had lower levels of antifibrotic miRNAs such as miR-144-3p, miR-142-3p, miR-34-b, and miR-503-5p that regulate cellular senescence, suggesting that EVs from diseased states are prosenescent and profibrotic [ 21 ].…”

Section: Evs In Ild Pathogenesismentioning

confidence: 99%

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Diagnostic and Therapeutic Applications of Extracellular Vesicles in Interstitial Lung Diseases

Ibrahim¹,

Ibrahim

Parimon

2021

Diagnostics

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Interstitial lung diseases (ILDs) are chronic irreversible pulmonary conditions with significant morbidity and mortality. Diagnostic approaches to ILDs are complex and multifactorial. Effective therapeutic interventions are continuously investigated and explored with substantial progress, thanks to advances in basic understanding and translational efforts. Extracellular vesicles (EVs) offer a new paradigm in diagnosis and treatment. This leads to two significant implications: new disease biomarker discovery that enables reliable diagnosis and disease assessment and the development of regenerative medicine therapeutics that target fibroproliferative processes in diseased lung tissue. In this review, we discuss the current understanding of the role of diseased tissue-derived EVs in the development of interstitial lung diseases, the utility of these EVs as diagnostic and prognostic tools, and the existing therapeutic utility of EVs. Furthermore, we review the potential therapeutic application of EVs derived from various cellular sources.

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Section: Extracellular Vesicles As Biomarkersmentioning

confidence: 91%

Section: Evs In Ild Pathogenesismentioning

confidence: 99%

Diagnostic and Therapeutic Applications of Extracellular Vesicles in Interstitial Lung Diseases

Ibrahim¹,

Ibrahim

Parimon

2021

Diagnostics

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“…101 Cellular senescence is a feature of the epithelial response to IPF. 102 EVs released from senescent cells have been linked to reduced reparative stem cell activity. 103 As intercellular communicators, EVs recruit fibroblasts to the ECM of the IPF lung.…”

Section: Idiopathic Pulmonary Fibrosismentioning

confidence: 99%

Role of extracellular vesicles in chronic lung disease

Trappe

Donnelly

McNally

et al. 2021

Thorax

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To explore the role of extracellular vesicles (EVs) in chronic lung diseases.EVs are emerging as mediators of intercellular communication and possible diagnostic markers of disease. EVs harbour cargo molecules including RNA, lipids and proteins that they transfer to recipient cells. EVs are intercellular communicators within the lung microenvironment. Due to their disease-specific cargoes, EVs have the promise to be all-in-one complex multimodal biomarkers. EVs also have potential as drug carriers in chronic lung disease.Descriptive discussion of key studies of EVs as contributors to disease pathology, as biomarkers and as potential therapies with a focus on chronic obstructive pulmonary disorder (COPD), cystic fibrosis (CF), asthma, idiopathic pulmonary fibrosis and lung cancer.We provide a broad overview of the roles of EV in chronic respiratory disease. Recent advances in profiling EVs have shown their potential as biomarker candidates. Further studies have provided insight into their disease pathology, particularly in inflammatory processes across a spectrum of lung diseases. EVs are on the horizon as new modes of drug delivery and as therapies themselves in cell-based therapeutics.EVs are relatively untapped sources of information in the clinic that can help further detail the full translational nature of chronic lung disorders.

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“…MiRNAs are major components of exosomes (Zeng et al, 2019). These molecules can bind to and regulate target mRNAs by inhibiting their translation or promoting their degradation and are widely involved in cell proliferation, apoptosis, development, differentiation, angiogenesis, and fibrosis (Kadota et al, 2020;Yao et al, 2020). Exosomes secreted by cancer-related fibroblasts and harboring miR-21, mir-378e and miR-143 can induce EMT in different breast cancer cell lines, and miR-21 can also promote EMT in renal tubular epithelial cells (Donnarumma et al, 2017).…”

Section: Exosomal Cargos and Epithelial Mesenchymal Transition Promotionmentioning

confidence: 99%

“…Exosomal let-7 from menstrual blood-derived endometrial stem cells alleviates lung fibrosis and alveolar epithelial cell damage in mice by regulating reactive oxygen species levels, mitochondrial DNA damage and NLRP3 inflammasome activation (Sun et al, 2019). Lung fibroblast-derived EVs from IPF patients were shown to increase mitochondrial reactive oxygen species levels and associated mitochondrial damage in lung epithelial cells, and these EVs were sown to contain elevated levels of miR-23b-3p and miR-494-3p (Kadota et al, 2020). Thus, the proliferation of fibroblasts, immunoregulatory pathways, and mitochondrial damage are novel mechanisms and promising targets for exosomal PF therapy.…”

Section: Novel Mechanisms Of Pf Mediated By Exosomesmentioning

confidence: 99%

Therapeutic Potential of Exosomes in Pulmonary Fibrosis

Xie

Zeng

2020

Front. Pharmacol.

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Pulmonary fibrosis is closely associated with the recruitment of fibroblasts from capillary vessels with damaged endothelial cells, the epithelial mesenchymal transition (EMT) of type II alveolar epithelial cells, and the transformation of fibroblasts to myofibroblasts. Recent studies suggest that EMT is a key factor in the pathogenesis of pulmonary fibrosis, as the disruption of EMT-related effector molecules can inhibit the occurrence and development of PF. With the numerous advancements made in molecular biology in recent years, researchers have discovered that exosomes and their cargos, such as miRNAs, lncRNAs, and proteins, can promote or inhibit the EMT, modulate the transformation of fibroblasts into myofibroblasts, contribute to the proliferation of fibroblasts and promote immunoregulatory and mitochondrial damage during pulmonary fibrosis. Exosomes are key factors regulating the differentiation of bone marrow mesenchymal stem cells (BMSCs) into myofibroblasts. Interestingly, exosomes derived from BMSCs under pathological and physiological conditions may promote or inhibit the EMT of type II alveolar epithelial cells and the transformation of fibroblasts into myofibroblasts to regulate pulmonary fibrosis. Thus, exosomes may become a new direction in the study of drugs for the treatment of pulmonary fibrosis.

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Extracellular Vesicles from Fibroblasts Induce Epithelial-Cell Senescence in Pulmonary Fibrosis

Cited by 79 publications

References 50 publications

Diagnostic and Therapeutic Applications of Extracellular Vesicles in Interstitial Lung Diseases

Diagnostic and Therapeutic Applications of Extracellular Vesicles in Interstitial Lung Diseases

Role of extracellular vesicles in chronic lung disease

Therapeutic Potential of Exosomes in Pulmonary Fibrosis

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