Long noncoding RNA-SNHG20 promotes silica-induced pulmonary fibrosis by miR-490-3p/TGFBR1 axis

Cheng, Demin; Xu, Qi; Liu, Yi; Li, Guanru; Sun, Wenqing; Ma, Dongyu; Ni, Chunhui

doi:10.1016/j.tox.2021.152683

Cited by 15 publications

(12 citation statements)

References 46 publications

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“…Thus, strategies to break this positive circle have been investigated to generate anti-fibrotic therapies [ 21 , 57 ]. For instance, miRNA let-7b represented a potential new target for the treatment of renal fibrosis in nephropathy by downregulating TGFBR1 [ 58 ], while long noncoding RNA-SNHG20 enhanced lung fibrosis via inhibiting miR-490 to up-regulate TGFBR1 [ 39 ]. Our findings also demonstrated that, for patients with shoulder stiffness, BMSC-EVs with their unique exosomal miRNAs constitution, targeted the TGFBR1 mRNA, confirming the pivotal role of this signaling pathway pathogenically and therapeutically.…”

Section: Discussionmentioning

confidence: 99%

“…All efforts were carried out to minimize animal suffering. We have submitted all relevant information of our experiments to the EV-TRACK knowledgebase according to EV-TRACK knowledgebase (ID: EV210463), which is the official standard for extracellular vesicle-related studies [ 39 ]. The whole experimental flow chart including treatments, timepoints, procedures, and test methods was presented in Supplemental Fig.…”

Section: Methodsmentioning

confidence: 99%

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Human bone marrow mesenchymal stem cell-derived extracellular vesicles inhibit shoulder stiffness via let-7a/Tgfbr1 axis

Luo

Sun

et al. 2022

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Human bone marrow mesenchymal stem cell-derived extracellular vesicles inhibit shoulder stiffness via let-7a/Tgfbr1 axis

Luo

Sun

et al. 2022

Bioactive Materials

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“…Then the tissues sections (5 μm) were subsequently stained with hematoxylin and eosin (H&E) to assess fibrosis. To evaluate the pathological changes of the lung tissues, a scoring system was used as previously described [ 34 ], lesion severity: 0 = zero/nothing, 1 = marginal, 2 = slight, 3 = moderate, 4 = severe, 5 = very severe; lesion distribution: 0 = absent, 1 = rare/occasional (10% of the lung area), 2 = spares/limited (10–25% of the lung area), 3 = moderate (25–50% of the lung area), 4 = extensive/widespread (50–75% of the lung area), 5 = very extensive/predominant (over 75% of the lung area).…”

Section: Methodsmentioning

confidence: 99%

Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling

Cheng

Wang

et al. 2021

J Transl Med

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Background Silicosis is one of the most common occupational pulmonary fibrosis caused by respirable silica-based particle exposure, with no ideal drugs at present. Metformin, a commonly used biguanide antidiabetic agent, could activate AMP-activated protein kinase (AMPK) to exert its pharmacological action. Therefore, we sought to investigate the role of metformin in silica-induced lung fibrosis. Methods The anti-fibrotic role of metformin was assessed in 50 mg/kg silica-induced lung fibrosis model. Silicon dioxide (SiO2)-stimulated lung epithelial cells/macrophages and transforming growth factor-beta 1 (TGF-β1)-induced differentiated lung fibroblasts were used for in vitro models. Results At the concentration of 300 mg/kg in the mouse model, metformin significantly reduced lung inflammation and fibrosis in SiO2-instilled mice at the early and late fibrotic stages. Besides, metformin (range 2–10 mM) reversed SiO2-induced cell toxicity, oxidative stress, and epithelial-mesenchymal transition process in epithelial cells (A549 and HBE), inhibited inflammation response in macrophages (THP-1), and alleviated TGF-β1-stimulated fibroblast activation in lung fibroblasts (MRC-5) via an AMPK-dependent pathway. Conclusions In this study, we identified that metformin might be a potential drug for silicosis treatment.

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“…Our data showed that the pulmonary function of mice was signi cantly decreased 56 days after silica instillation, and CT imaging of the mouse chest and H&E staining showed extensive alveolar structure collapse and excessive collagen deposition, indicating well-established PF. Previous reports have also pointed out that PF develops 56 days after silica intratracheal instillation (Cheng et al, 2021a;Dinh et al, 2020;Liu et al, 2017). Therefore, we collected data and samples 56 days after silica treatment in our study.…”

Section: Discussionmentioning

confidence: 96%

Macrophage-derived GPNMB Trapped by Fibrotic Extracellular Matrix Promotes Pulmonary Fibrosis

Wang¹,

Zhang²,

Yuan

et al. 2022

Preprint

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Pulmonary fibrosis (PF) is a form of progressive lung disease characterized by chronic inflammation and excessive extracellular matrix (ECM) deposition. The pulmonary ECM undergoes profound changes during fibrosis. However, the protein changes that occur in fibrotic ECM during silica-induced progressive PF and their contribution to fibrosis progression are unclear. Here, we established a model of progressive PF induced by silica, observed the effect of fibrotic ECM on normal fibroblast activation and explored the possible mechanism. Proteomic analysis of the ECM revealed that obvious changes in the expression of ECM components and ECM remodeling occurred. Single-cell RNA sequencing (scRNA-seq) combined with spatial transcriptomics revealed that during transport, macrophage-derived glycoprotein nonmetastatic melanoma protein B (GPNMB) captured by fibrotic ECM may activate resident normal fibroblasts around fibrotic foci. Functional experiments showed activation of normal fibroblasts in fibrotic ECM, which was alleviated by GPNMB-neutralizing antibodies or macrophage deletion in the ECM of silica-instilled mice, implying that macrophage-derived GPNMB may contribute to progressive PF. Transcriptome analysis showed that the Serpinb2 expression level was increased in fibroblasts in fibrotic ECM, and the expression of CD44, a cell receptor for GPNMB, was increased in mice after silica instillation according to scRNA-seq combined with spatial transcriptomics. Therefore, macrophage-derived GPNMB is trapped by fibrotic ECM during transport and may activate fibroblasts via the CD44/Serpinb2 pathway, leading to further development of fibrosis.

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Long noncoding RNA-SNHG20 promotes silica-induced pulmonary fibrosis by miR-490-3p/TGFBR1 axis

Cited by 15 publications

References 46 publications

Human bone marrow mesenchymal stem cell-derived extracellular vesicles inhibit shoulder stiffness via let-7a/Tgfbr1 axis

Human bone marrow mesenchymal stem cell-derived extracellular vesicles inhibit shoulder stiffness via let-7a/Tgfbr1 axis

Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling

Macrophage-derived GPNMB Trapped by Fibrotic Extracellular Matrix Promotes Pulmonary Fibrosis

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