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Club cell-specific role of programmed cell death 5 in pulmonary fibrosis

 Soo-Yeon Park  ;  Jung Yeon Hong  ;  Soo Yeon Lee  ;  Seung-Hyun Lee  ;  Mi Jeong Kim  ;  Soo Yeon Kim  ;  Kyung Won Kim  ;  Hyo Sup Shim  ;  Moo Suk Park  ;  Chun Geun Lee  ;  Jack A Elias  ;  Myung Hyun Sohn  ;  Ho-Geun Yoon 
 NATURE COMMUNICATIONS, Vol.12(1) : 2923, 2021-05 
Journal Title
Issue Date
Aged ; Animals ; Apoptosis Regulatory Proteins / deficiency ; Apoptosis Regulatory Proteins / genetics* ; Apoptosis Regulatory Proteins / metabolism ; Bronchioles / metabolism ; Bronchioles / pathology ; Cell Line ; Disease Models, Animal ; Epithelial Cells / metabolism ; Epithelial Cells / pathology ; Female ; Gene Expression ; Gene Knockdown Techniques ; Humans ; Idiopathic Pulmonary Fibrosis / genetics* ; Idiopathic Pulmonary Fibrosis / pathology* ; Lung / metabolism ; Lung / pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Middle Aged ; Neoplasm Proteins / deficiency ; Neoplasm Proteins / genetics* ; Neoplasm Proteins / metabolism ; Respiratory Mucosa / metabolism ; Respiratory Mucosa / pathology ; Signal Transduction ; Smad3 Protein / metabolism ; Transforming Growth Factor beta / metabolism ; p38 Mitogen-Activated Protein Kinases / metabolism
Idiopathic pulmonary fibrosis (IPF) causes progressive fibrosis and worsening pulmonary function. Prognosis is poor and no effective therapies exist. We show that programmed cell death 5 (PDCD5) expression is increased in the lungs of patients with IPF and in mouse models of lung fibrosis. Lung fibrosis is significantly diminished by club cell-specific deletion of Pdcd5 gene. PDCD5 mediates β-catenin/Smad3 complex formation, promoting TGF-β-induced transcriptional activation of matricellular genes. Club cell Pdcd5 knockdown reduces matricellular protein secretion, inhibiting fibroblast proliferation and collagen synthesis. Here, we demonstrate the club cell-specific role of PDCD5 as a mediator of lung fibrosis and potential therapeutic target for IPF.
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1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Won(김경원) ORCID logo https://orcid.org/0000-0003-4529-6135
Kim, Mi Jeong(김미정) ORCID logo https://orcid.org/0000-0002-0758-7145
Kim, Soo Yeon(김수연) ORCID logo https://orcid.org/0000-0003-4965-6193
Park, Moo Suk(박무석) ORCID logo https://orcid.org/0000-0003-0820-7615
Park, Soo Yeon(박수연) ORCID logo https://orcid.org/0000-0003-3743-9554
Sohn, Myung Hyun(손명현) ORCID logo https://orcid.org/0000-0002-2478-487X
Shim, Hyo Sup(심효섭) ORCID logo https://orcid.org/0000-0002-5718-3624
Yoon, Ho Geun(윤호근) ORCID logo https://orcid.org/0000-0003-2718-3372
Lee, Soo Yeon(이수연)
Lee, Seung Hyun(이승현) ORCID logo https://orcid.org/0000-0001-7549-9430
Hong, Jung Yeon(홍정연) ORCID logo https://orcid.org/0000-0003-0406-9956
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