Anti-PD-L1 antibody alleviates pulmonary fibrosis by inducing autophagy via inhibition of the PI3K/Akt/mTOR pathway

Anti-fibrosis effect for Hirsutella sinensis mycelium based on inhibition of mTOR p70S6K phosphorylation

Innate Immunity ◽

10.1177/1753425917726361 ◽

2017 ◽

Vol 23 (7) ◽

pp. 615-624 ◽

Cited By ~ 5

Author(s):

Huimin Yue ◽

Yarong Zhao ◽

Haining Wang ◽

Feiya Ma ◽

Fei Liu ◽

...

Keyword(s):

Pulmonary Fibrosis ◽

Lung Fibrosis ◽

Molecular Mechanisms ◽

Histopathological Examination ◽

Smooth Muscle Actin ◽

A549 Cells ◽

Mtor Pathway ◽

Cordyceps Sinensis ◽

Tgf Β1

Hirsutella sinensis, cultured in vitro, is an attractive substitute for Cordyceps sinensis as health supplement. The aim of this study was to demonstrate whether H. sinensis mycelium (HSM) attenuates murine pulmonary fibrosis induced by bleomycin and to explore the underlying molecular mechanisms. Using lung fibrosis modle induced by intratracheal instillation of bleomycin (BLM; 4 mg/kg), we observed that the administration of HSM reduced HYP, TGF-β1 and the production of several pro-fibrosis cytokines (α-smooth muscle actin, fibronectin and vimentin) in fibrotic mice lung sections. Histopathological examination of lung tissues also demonstrated that HSM improved BLM-induced pathological damage. Concurrently, HSM supplementation markedly reduced the chemotaxis of alveolar macrophages and potently suppressed the expression of inflammatory cytokines. Also, HSM influenced Th1/Th2 and Th17/Treg imbalance and blocked the phosphorylation of mTOR pathway in vivo. Alveolar epithelial A549 cells acquired a mesenchymal phenotype and an increased expression of myofibroblast markers of differentiation (vimentin and fibronectin) after treatment with TGF-β1. HSM suppressed these markers and blocked the phosphorylation of mTOR pathway in vitro. The results provide evidence supporting the use of HSM in the intervention of pulmonary fibrosis and suggest that HSM is a potential therapeutic agent for lung fibrosis.

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Leptin promotes pulmonary fibrosis development by inhibiting autophagy via PI3K/Akt/mTOR pathway

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2018.03.039 ◽

2018 ◽

Vol 498 (3) ◽

pp. 660-666 ◽

Cited By ~ 26

Author(s):

Xianhua Gui ◽

Hongwei Chen ◽

Hourong Cai ◽

Lingyun Sun ◽

Luo Gu

Keyword(s):

Pulmonary Fibrosis ◽

Mtor Pathway

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N6-methyladenosine-dependent primary microRNA-126 processing activated PI3K-AKT-mTOR pathway drove the development of pulmonary fibrosis induced by nanoscale carbon black particles in rats

Nanotoxicology ◽

10.1080/17435390.2019.1661041 ◽

2019 ◽

Vol 14 (1) ◽

pp. 1-20 ◽

Cited By ~ 6

Author(s):

Bin Han ◽

Chen Chu ◽

Xuan Su ◽

Ning Zhang ◽

Lixiao Zhou ◽

...

Keyword(s):

Pulmonary Fibrosis ◽

Carbon Black ◽

Mtor Pathway

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Thy-1 depletion and integrin β3 upregulation-mediated PI3K-Akt-mTOR pathway activation inhibits lung fibroblast autophagy in lipopolysaccharide-induced pulmonary fibrosis

Laboratory Investigation ◽

10.1038/s41374-019-0281-2 ◽

2019 ◽

Vol 99 (11) ◽

pp. 1636-1649 ◽

Cited By ~ 4

Author(s):

Hanxi Wan ◽

Tingting Xie ◽

Qiaoyi Xu ◽

Xiaoting Hu ◽

Shunpeng Xing ◽

...

Keyword(s):

Pulmonary Fibrosis ◽

Lung Fibroblast ◽

Mtor Pathway ◽

Integrin Β3 ◽

Pathway Activation

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Anti-PD-L1 Antibody Alleviate Pulmonary Fibrosis by Inducing Autophagy via Inhibition of the PI3K/Akt/mTOR Pathway

SSRN Electronic Journal ◽

10.2139/ssrn.3947644 ◽

2021 ◽

Author(s):

Ye Lu ◽

Wenshan Zhong ◽

Yuanyuan Liu ◽

Weimou Chen ◽

Jinming Zhang ◽

...

Keyword(s):

Pulmonary Fibrosis ◽

Mtor Pathway

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Quantitative Microscopic Comparison of the Organization of the Lung in Transgenic Mice Expressing Transforming Growth Factor-α (TGF-α)

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100162533 ◽

1996 ◽

Vol 54 ◽

pp. 14-15

Author(s):

C. G. Plopper ◽

C. Helton ◽

A. J. Weir ◽

J. A. Whitsett ◽

T. R. Korfhagen

Keyword(s):

Growth Factor ◽

Pulmonary Fibrosis ◽

Transgenic Mice ◽

Blood Vessels ◽

Lung Parenchyma ◽

Lung Maturation ◽

Alveolar Air ◽

Parenchymal Tissue ◽

Air Space ◽

Conducting Airways

A wide variety of growth factors are thought to be involved in the regulation of pre- and postnatal lung maturation, including factors which bind to the epidermal growth factor receptor. Marked pulmonary fibrosis and enlarged alveolar air spaces have been observed in lungs of transgenic mice expressing human TGF-α under control of the 3.7 KB human SP-C promoter. To test whether TGF-α alters lung morphogenesis and cellular differentiation, we examined morphometrically the lungs of adult (6-10 months) mice derived from line 28, which expresses the highest level of human TGF-α transcripts among transgenic lines. Total volume of lungs (LV) fixed by airway infusion at standard pressure was similar in transgenics and aged-matched non-transgenic mice (Fig. 1). Intrapulmonary bronchi and bronchioles made up a smaller percentage of LV in transgenics than in non-transgenics (Fig. 2). Pulmonary arteries and pulmonary veins were a smaller percentage of LV in transgenic mice than in non-transgenics (Fig. 3). Lung parenchyma (lung tissue free of large vessels and conducting airways) occupied a larger percentage of LV in transgenics than in non-transgenics (Fig. 4). The number of generations of branching in conducting airways was significantly reduced in transgenics as compared to non-transgenic mice. Alveolar air space size, as measured by mean linear intercept, was almost twice as large in transgenic mice as in non-transgenics, especially when different zones within the lung were compared (Fig. 5). Alveolar air space occupied a larger percentage of the lung parenchyma in transgenic mice than in non-transgenic mice (Fig. 6). Collagen abundance was estimated in histological sections as picro-Sirius red positive material by previously-published methods. In intrapulmonary conducting airways, collagen was 4.8% of the wall in transgenics and 4.5% of the wall in non-transgenic mice. Since airways represented a smaller percentage of the lung in transgenics, the volume of interstitial collagen associated with airway wall was significantly less. In intrapulmonary blood vessels, collagen was 8.9% of the wall in transgenics and 0.7% of the wall in non-transgenics. Since blood vessels were a smaller percentage of the lungs in transgenics, the volume of collagen associated with the walls of blood vessels was five times greater. In the lung parenchyma, collagen was 51.5% of the tissue volume in transgenics and 21.2% in non-transgenics. Since parenchyma was a larger percentage of lung volume in transgenics, but the parenchymal tissue was a smaller percent of the volume, the volume of collagen associated with parenchymal tissue was only slightly greater. We conclude that overexpression of TGF-α during lung maturation alters many aspects of lung development, including branching morphogenesis of the airways and vessels and alveolarization in the parenchyma. Further, the increases in visible collagen previously associated with pulmonary fibrosis due to the overexpression of TGF-α are a result of actual increases in amounts of collagen and in a redistribution of collagen within compartments which results from morphogenetic changes. These morphogenetic changes vary by lung compartment. Supported by HL20748, ES06700 and the Cystic Fibrosis Foundation.

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