ID 60828
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Kawara, Akina Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University
Mizuta, Ryo Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University
Fujisawa, Masayoshi Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University ORCID
Ito, Toshihiro Department of Immunology, Nara Medical University
Li, Chunning Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University
Nakamura, Kaoru Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University
Sun, Cuiming Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University
Kuwabara, Masaki Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University
Kitabatake, Masahiro Department of Immunology, Nara Medical University
Yoshimura, Teizo Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University Kaken ID
Matsukawa, Akihiro Department of Pathology and Experimental Medicine, Graduated School of Medicine, Dentistry and Pharmaceutical Science, Okayama University ORCID Kaken ID publons researchmap
Abstract
The mitogen-activated protein kinase (MAPK) pathways are involved in many cellular processes, including the development of fibrosis. Here, we examined the role of Sprouty-related EVH-1-domain-containing protein (Spred) 2, a negative regulator of the MAPK-ERK pathway, in the development of bleomycin (BLM)-induced pulmonary fibrosis (PF). Compared to WT mice, Spred2−/− mice developed milder PF with increased proliferation of bronchial epithelial cells. Spred2−/− lung epithelial cells or MLE-12 cells treated with spred2 siRNA proliferated faster than control cells in vitro. Spred2−/− and WT macrophages produced similar levels of TNFα and MCP-1 in response to BLM or lipopolysaccharide and myeloid cell-specific deletion of Spred2 in mice had no effect. Spred2−/− fibroblasts proliferated faster and produced similar levels of MCP-1 compared to WT fibroblasts. Spred2 mRNA was almost exclusively detected in bronchial epithelial cells of naïve WT mice and it accumulated in approximately 50% of cells with a characteristic of Clara cells, 14 days after BLM treatment. These results suggest that Spred2 is involved in the regulation of tissue repair after BLM-induced lung injury and increased proliferation of lung bronchial cells in Spred2−/− mice may contribute to faster tissue repair. Thus, Spred2 may present a new therapeutic target for the treatment of PF.
Keywords
Cell signalling
Mechanisms of disease
Published Date
2020-10-05
Publication Title
Scientific Reports
Volume
volume10
Issue
issue1
Publisher
Nature
Start Page
16490
ISSN
2045-2322
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
Copyright Holders
© The Author(s) 2020
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publisher
PubMed ID
DOI
Web of Science KeyUT
Related Url
isVersionOf https://doi.org/10.1038/s41598-020-73752-3
License
http://creat iveco mmons .org/licen ses/by/4.0/
Funder Name
Japan Society for the Promotion of Science
助成番号
25293095
16K15258