Senescence in Pulmonary Fibrosis: Between Aging and Exposure

Venosa, Alessandro

doi:10.3389/fmed.2020.606462

Cited by 37 publications

(35 citation statements)

References 367 publications

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“…Compromised self-repair function of alveolar epithelial cells (AECs) after exposure to a micro-injury environment is thought to initiate IPF [ 4 ]. Recently, senescence was identified as an important cause of the dampened AECs repair function in IPF, resulting decreased AECs regeneration and repair [ 5 , 6 ]. Currently, the cause and regulatory mechanism of AECs senescence are unclear.…”

Section: Introductionmentioning

confidence: 99%

Regulation of the IGF1 signaling pathway is involved in idiopathic pulmonary fibrosis induced by alveolar epithelial cell senescence and core fucosylation

Sun

Jing

Yang

et al. 2021

Aging

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Idiopathic pulmonary fibrosis (IPF) mainly occurs in elderly people over the age of sixty. IPF pathogenesis is associated with alveolar epithelial cells (AECs) senescence. Activation of PI3K/AKT signaling induced by insulin-like growth factor 1 (IGF1) participates in AEC senescence and IPF by releasing CTGF, TGF-β1, and MMP9. Our previous study demonstrated that core fucosylation (CF) modification, catalyzed by a specific core fucosyltransferase (FUT8) can regulate the activation of multiple signaling pathways, and inhibiting CF can alleviate pulmonary fibrosis in mice induced by bleomycin. However, whether CF is involved in IGF1-mediated AEC senescence in IPF remains unclear. In this study, we found that the IGF1/PI3K/AKT signaling pathway was activated in IPF lung tissue. Meanwhile, CF was present in senescent AECs. We also showed that IGF1 could induce AECs senescence with enhanced CF in vivo and in vitro . Inhibiting CF alleviated AECs senescence and pulmonary fibrosis induced by IGF1. In addition, activation of IGF1/PI3K/AKT signaling depends on CF. In conclusion, this study confirmed that CF is an important target regulating the IGF1 signaling pathway in AEC senescence and IPF, which might be a candidate target to treat IPF in the future.

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Section: Introductionmentioning

confidence: 99%

Regulation of the IGF1 signaling pathway is involved in idiopathic pulmonary fibrosis induced by alveolar epithelial cell senescence and core fucosylation

Sun

Jing

Yang

et al. 2021

Aging

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“…Multiple studies have confirmed the fibrogenic potential of certain types of MWCNTs, but only a few studies have examined the effects of MWCNTs on cellular senescence [ 24 , 25 ]. Pulmonary fibrosis is a disease of aging and senescence with a median age of diagnosis of 66 years of age [ 26 , 27 ]. This study sought to evaluate whether exposure to MWCNTs would lead to cellular senescence and pro-fibrotic phenotypes in human bronchial epithelial cells (BEAS-2B).…”

Section: Discussionmentioning

confidence: 99%

Multi-Walled Carbon Nanotubes (MWCNTs) Cause Cellular Senescence in TGF-β Stimulated Lung Epithelial Cells

Lucas

Wang

Muthumalage

et al. 2021

Toxics

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Multi-walled carbon nanotubes are engineered nanomaterials (ENMs) that have a fiber-like structure which may be a concern for the development of cellular senescence. Premature senescence, a state of irreversible cell cycle arrest, is implicated in the pathogenesis of chronic lung diseases such as pulmonary fibrosis (PF). However, the crosstalk between downstream pathways mediating fibrotic and senescent responses of MWCNTs is not well-defined. Here, we exposed human bronchial epithelial cells (BEAS-2B) to MWCNTs for up to 72 h and demonstrate that MWCNTs increase reactive oxygen species (ROS) production accompanied by inhibition of cell proliferation. In addition, MWCNT exposure resulted in the increase of p21 protein abundance and senescence associated β-galactosidase (SA β-gal) activity. We also determined that co-exposure with the cytokine, transforming growth factor-β (TGF-β) exacerbated cellular senescence indicated by increased protein levels of p21, p16, and γH2A.X. Furthermore, the production of fibronectin and plasminogen activator inhibitor (PAI-1) was significantly elevated with the co-exposure compared to MWCNT or TGF-β alone. Together, our study suggests that the cellular senescence potential of MWCNTs may be enhanced by pro-fibrotic mediators, such as TGF-β in the surrounding microenvironment.

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“…Multiple studies have confirmed the fibrogenic potential of certain types of MWCNTs, but only a few studies have examined the effects of MWCNTs on cellular senescence [15,16]. Pulmonary fibrosis is a disease of aging and senescence with a median age of diagnosis of 66 years of age [18,19]. This study sought to evaluate whether exposure to MWCNTs would lead to cellular senescence and pro-fibrotic phenotypes in human bronchial epithelial cells (BEAS2B).…”

Section: Discussionmentioning

confidence: 99%

Multi-Walled Carbon Nanotubes (MWCNTs) Cause Cellular Senescence in TGF-β Stimulated Lung Epithelial Cells

Lucas

Wang

Muthumalage

et al. 2021

Preprint

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Multi-walled carbon nanotubes are engineered nanomaterials (ENMs) that have a fiber-like structure which may be a concern for the development of cellular senescence. Premature senes-cence, a state of irreversible cell cycle arrest, is implicated in the pathogenesis of chronic lung dis-eases such as pulmonary fibrosis (PF). However, the crosstalk between downstream pathways mediating fibrotic and senescent responses of MWCNTs is not well defined. Here, we exposed human bronchial epithelial cells (BEAS2B) to MWCNTs for up to 72 hours and demonstrate that MWCNTs increase reactive oxygen species production (ROS) accompanied by inhibition of cell growth and proliferation. In addition, exposure resulted in the increase of p21 protein and senes-cence associated β-galactosidase (SA β-gal) activity. We also determined that co-exposure with the cytokine, transforming growth factor-β (TGF-β) exacerbated cellular senescence indicated by increased protein levels of p21, p16, and γH2A.X Furthermore, the production of fibronectin and plasminogen activator inhibitor (PAI-1) was significantly elevated with the co-exposure compared to MWCNTs or TGF-β alone. Together, this suggests that the senescence potential of MWCNTs may be enhanced by pro-fibrotic mediators in the surrounding microenvironment.

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Senescence in Pulmonary Fibrosis: Between Aging and Exposure

Cited by 37 publications

References 367 publications

Regulation of the IGF1 signaling pathway is involved in idiopathic pulmonary fibrosis induced by alveolar epithelial cell senescence and core fucosylation

Regulation of the IGF1 signaling pathway is involved in idiopathic pulmonary fibrosis induced by alveolar epithelial cell senescence and core fucosylation

Multi-Walled Carbon Nanotubes (MWCNTs) Cause Cellular Senescence in TGF-β Stimulated Lung Epithelial Cells

Multi-Walled Carbon Nanotubes (MWCNTs) Cause Cellular Senescence in TGF-β Stimulated Lung Epithelial Cells

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