Earthworm extract attenuates silica-induced pulmonary fibrosis through Nrf2-dependent mechanisms

Yang, Jingjin; Wang, Ting; Li, Yan; Yao, Wenxi; Ji, Xiaoming; Wu, Qiuyun; Han, Lei; Han, Renfang; Yan, Wei; Yuan, Jiali; Ni, Chunhui

doi:10.1038/labinvest.2016.101

Cited by 29 publications

(21 citation statements)

References 55 publications

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“…Therefore, the endogenous anti‐inflammatory and antioxidative reactions will be activated in response to the inflammation and redox imbalance triggered by particles exposure. Besides that, the epithelial cells of the conducting airways activation by cytokines after interaction with the inhaled particles also plays an important role in the procession of particles‐induced lung injury and tissue repair . Transforming growth factor (TGF) β1 is the most recognized isoform of TGFβ superfamily implicated in respiratory diseases, which is central to the profibrotic switch, activation of myofibroblasts and matrix production, inhibition of lung epithelial cells' proliferation, and is upregulated in lung inflammation .…”

Section: Introductionmentioning

confidence: 99%

Vitamin D protects against particles‐caused lung injury through induction of autophagy in an Nrf2‐dependent manner

Tao

Zhang

Xue

et al. 2019

Environmental Toxicology

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Fine particulate matter is a well-known air pollutant threatening public health. Studies have confirmed long-term exposure to the particles could decrease the pulmonary function, induce asthma exacerbation, and chronic obstructive pulmonary disease, as well as increase the incidence and mortality of lung cancer. A clinical study has explored that the prevalence and risks of vitamin D (VD) deficiency in various chronic disease and toxins induced tissue damage. Our current study aimed to explore the mechanism and further therapeutic potential of VD administration to ameliorate fine particles exposure induced pulmonary damage in vivo and in vitro. To elucidate the effects and mechanisms of VD in particles-induced pulmonary damage, a murine model was established with fine particles intratracheal instillation along with VD intramuscular injection. Our study demonstrated that treatment with VD attenuated particles-induced pulmonary damage and promoted tissue repair by repressing of TGFβ1 signaling pathway and upregulation of MMP9 expression. VD treatment could also regulate the autophagy-related signals along with activation of Nrf2 transcription factor. Furthermore, the results from the in vitro study demonstrated that VD protected against particles-induced cells' damage through the induction of autophagy in an Nrf2-dependent manner. VD treatment caused the degradation of P62 and its bound Keap1, which decreased the Nrf2 ubiquitination and increasing its protein stability. Our work explored a novel potential mechanism in the protection of VD in particlesinduced pulmonary injury and tissue repair, and could further bring insights into exploring antifine particles exposure caused inflammation among other natural products and contributes to inflammation disease medical therapies. K E Y W O R D Sautophagy, fine particulate matter, Nrf2 signals, TGFβ1, vitamin D

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Section: Introductionmentioning

confidence: 99%

Vitamin D protects against particles‐caused lung injury through induction of autophagy in an Nrf2‐dependent manner

Tao

Zhang

Xue

et al. 2019

Environmental Toxicology

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“…However, few studies have been conducted to investigate the direct relationship among the mitochondrial dysfunction, mitophagy, and silicosis. Several studies indicated that silica disturbed mitochondrial energy generation and activated the mitochondrial apoptotic pathway in macrophage (RAW264.7) and epithelial cell (HBE, A549) [ 8 , 9 , 10 ]. Therefore, it is possible that aberrant mitochondria and mitophagy activity participate in the pathogenesis of silicosis, but the exact mechanisms by which mitophagy is modulated under silica exposure remains unknown.…”

Section: Introductionmentioning

confidence: 99%

miR-1224-5p Mediates Mitochondrial Damage to Affect Silica-Induced Pulmonary Fibrosis by Targeting BECN1

Liu

et al. 2017

IJMS

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Silicosis is associated with fibroblast proliferation and extracellular matrix deposition in lung tissues. The dysregulation of miR-1224-5p has been implicated in several human cancers; however, the expression and function of miR-1224-5p in silicosis is unknown. The mitochondrial dysfunctions play critical roles in some diseases, but how these processes are regulated in silicosis remains limited. Here, we explored the role of miR-1224-5p in a mouse model of silicosis. We showed that the expression of miR-1224-5p is increased both in lung tissues of silica-induced pulmonary fibrosis and fibroblasts exposed to TGF-β1. Repression of miR-1224-5p expression attenuated silica-induced fibrotic progression in vivo and TGF-β1-induced myofibroblast differentiation in vitro. Additionally, we demonstrated that miR-1224-5p facilitated silica-induced pulmonary fibrosis primarily by repressing one of target genes, BECN1, thereby blocking PARK2 translocation to mitochondria and inducing the accumulation of damaged mitochondria. Furthermore, the activation of PDGFR signal mediated by mitochondrial damage and insufficient mitophagy resulted in myofibroblast differentiation. Collectively, these data indicated that miR-1224-5p exerts key functions in silica-induced pulmonary fibrosis and may represent a potential therapeutic target for silicosis.

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“…These include the induction of inflammatory cytokines and modulation of transcription factors or non-coding RNAs (ncRNAs) Yang et al, 2016;Han et al, 2016). Meanwhile, biological events, such as autoimmunity, angiogenesis, and epithelial-mesenchymal transition (EMT) are involved in different stages of silicosis (Leung et al, 2012).…”

Section: A C C E P T E Dmentioning

confidence: 99%

Profiling long non-coding RNA changes in silica-induced pulmonary fibrosis in rat

Sai¹,

Yu²,

Bo³

et al. 2019

Toxicology Letters

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 On day 28, lung fibrosis in silica-induced rats was confirmed.  Silica induces changes in 682 lncRNAs (300 upregulated, 382 downregulated).  The predicted target mRNAs of lncRNAs of silicosis involves in 13 pathways.  "Proteoglycans in cancer" signaling pathway in pulmonary fibrosis is valuable to study.  LncRNA-miRNA-mRNA ceRNA network may play an important role in pulmonary fibrosis.

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Earthworm extract attenuates silica-induced pulmonary fibrosis through Nrf2-dependent mechanisms

Cited by 29 publications

References 55 publications

Vitamin D protects against particles‐caused lung injury through induction of autophagy in an Nrf2‐dependent manner

Vitamin D protects against particles‐caused lung injury through induction of autophagy in an Nrf2‐dependent manner

miR-1224-5p Mediates Mitochondrial Damage to Affect Silica-Induced Pulmonary Fibrosis by Targeting BECN1

Profiling long non-coding RNA changes in silica-induced pulmonary fibrosis in rat

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