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LRRK2 plays essential roles in maintaining lung homeostasis and preventing the development of pulmonary fibrosis
by
Wu, Tao
, Li, Xiaoguang
, Hu, Xiaoyu
, Wu, Li
, Lv, Jiaoyan
, Tian, Yujie
, Su, Ziyan
, Zhang, Jianhong
in
Alveolar Epithelial Cells - immunology
/ Alveolar Epithelial Cells - metabolism
/ Alveolar Epithelial Cells - pathology
/ Alveoli
/ Animals
/ Antibiotics, Antineoplastic - toxicity
/ Autophagy
/ Biological Sciences
/ Bleomycin
/ Bleomycin - toxicity
/ CCR2 protein
/ Fibrosis
/ Homeostasis
/ Idiopathic Pulmonary Fibrosis - chemically induced
/ Idiopathic Pulmonary Fibrosis - metabolism
/ Idiopathic Pulmonary Fibrosis - pathology
/ Idiopathic Pulmonary Fibrosis - prevention & control
/ Immune response
/ Immunity, Innate
/ Immunology and Inflammation
/ Innate immunity
/ Kinases
/ Leucine
/ Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - physiology
/ LRRK2 protein
/ Lung - immunology
/ Lung - metabolism
/ Lung - pathology
/ Lung diseases
/ Lungs
/ Macrophages
/ Macrophages - immunology
/ Macrophages - metabolism
/ Macrophages - pathology
/ Male
/ Mice
/ Mice, Inbred C57BL
/ Mice, Knockout
/ Monocyte chemoattractant protein 1
/ Perturbation
/ Phagocytosis
/ Pulmonary fibrosis
/ Respiratory diseases
/ Senescence
/ Signal Transduction
2021
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LRRK2 plays essential roles in maintaining lung homeostasis and preventing the development of pulmonary fibrosis
by
Wu, Tao
, Li, Xiaoguang
, Hu, Xiaoyu
, Wu, Li
, Lv, Jiaoyan
, Tian, Yujie
, Su, Ziyan
, Zhang, Jianhong
in
Alveolar Epithelial Cells - immunology
/ Alveolar Epithelial Cells - metabolism
/ Alveolar Epithelial Cells - pathology
/ Alveoli
/ Animals
/ Antibiotics, Antineoplastic - toxicity
/ Autophagy
/ Biological Sciences
/ Bleomycin
/ Bleomycin - toxicity
/ CCR2 protein
/ Fibrosis
/ Homeostasis
/ Idiopathic Pulmonary Fibrosis - chemically induced
/ Idiopathic Pulmonary Fibrosis - metabolism
/ Idiopathic Pulmonary Fibrosis - pathology
/ Idiopathic Pulmonary Fibrosis - prevention & control
/ Immune response
/ Immunity, Innate
/ Immunology and Inflammation
/ Innate immunity
/ Kinases
/ Leucine
/ Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - physiology
/ LRRK2 protein
/ Lung - immunology
/ Lung - metabolism
/ Lung - pathology
/ Lung diseases
/ Lungs
/ Macrophages
/ Macrophages - immunology
/ Macrophages - metabolism
/ Macrophages - pathology
/ Male
/ Mice
/ Mice, Inbred C57BL
/ Mice, Knockout
/ Monocyte chemoattractant protein 1
/ Perturbation
/ Phagocytosis
/ Pulmonary fibrosis
/ Respiratory diseases
/ Senescence
/ Signal Transduction
2021
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LRRK2 plays essential roles in maintaining lung homeostasis and preventing the development of pulmonary fibrosis
by
Wu, Tao
, Li, Xiaoguang
, Hu, Xiaoyu
, Wu, Li
, Lv, Jiaoyan
, Tian, Yujie
, Su, Ziyan
, Zhang, Jianhong
in
Alveolar Epithelial Cells - immunology
/ Alveolar Epithelial Cells - metabolism
/ Alveolar Epithelial Cells - pathology
/ Alveoli
/ Animals
/ Antibiotics, Antineoplastic - toxicity
/ Autophagy
/ Biological Sciences
/ Bleomycin
/ Bleomycin - toxicity
/ CCR2 protein
/ Fibrosis
/ Homeostasis
/ Idiopathic Pulmonary Fibrosis - chemically induced
/ Idiopathic Pulmonary Fibrosis - metabolism
/ Idiopathic Pulmonary Fibrosis - pathology
/ Idiopathic Pulmonary Fibrosis - prevention & control
/ Immune response
/ Immunity, Innate
/ Immunology and Inflammation
/ Innate immunity
/ Kinases
/ Leucine
/ Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - physiology
/ LRRK2 protein
/ Lung - immunology
/ Lung - metabolism
/ Lung - pathology
/ Lung diseases
/ Lungs
/ Macrophages
/ Macrophages - immunology
/ Macrophages - metabolism
/ Macrophages - pathology
/ Male
/ Mice
/ Mice, Inbred C57BL
/ Mice, Knockout
/ Monocyte chemoattractant protein 1
/ Perturbation
/ Phagocytosis
/ Pulmonary fibrosis
/ Respiratory diseases
/ Senescence
/ Signal Transduction
2021
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LRRK2 plays essential roles in maintaining lung homeostasis and preventing the development of pulmonary fibrosis
Journal Article
LRRK2 plays essential roles in maintaining lung homeostasis and preventing the development of pulmonary fibrosis
2021
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Overview
Perturbation of lung homeostasis is frequently associated with progressive and fatal respiratory diseases, such as pulmonary fibrosis. Leucine-rich repeat kinase 2 (LRRK2) is highly expressed in healthy lungs, but its functions in lung homeostasis and diseases remain elusive. Herein, we showed that LRRK2 expression was clearly reduced in mammalian fibrotic lungs, and LRRK2-deficient mice exhibited aggravated bleomycin-induced pulmonary fibrosis. Furthermore, we demonstrated that in bleomycin-treated mice, LRRK2 expression was dramatically decreased in alveolar type II epithelial (AT2) cells, and its deficiency resulted in profound dysfunction of AT2 cells, characterized by impaired autophagy and accelerated cellular senescence. Additionally, LRRK2-deficient AT2 cells showed a higher capacity of recruiting profibrotic macrophages via the CCL2/CCR2 signaling, leading to extensive macrophage-associated profibrotic responses and progressive pulmonary fibrosis. Taken together, our study demonstrates that LRRK2 plays a crucial role in preventing AT2 cell dysfunction and orchestrating the innate immune responses to protect against pulmonary fibrosis.
Publisher
National Academy of Sciences
Subject
Alveolar Epithelial Cells - immunology
/ Alveolar Epithelial Cells - metabolism
/ Alveolar Epithelial Cells - pathology
/ Alveoli
/ Animals
/ Antibiotics, Antineoplastic - toxicity
/ Fibrosis
/ Idiopathic Pulmonary Fibrosis - chemically induced
/ Idiopathic Pulmonary Fibrosis - metabolism
/ Idiopathic Pulmonary Fibrosis - pathology
/ Idiopathic Pulmonary Fibrosis - prevention & control
/ Kinases
/ Leucine
/ Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 - physiology
/ Lungs
/ Male
/ Mice
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