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Involvement of midkine in the development of pulmonary fibrosis

Midkine is a low‐molecular‐weight heparin‐binding protein that is strongly expressed mainly in the midgestation period and has various physiological activities such as in development and cell migration. Midkine has been reported to be strongly expressed in cancer cells and in inflammation and repair...

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Autores principales: Misa, Kenichi, Tanino, Yoshinori, Wang, Xintao, Nikaido, Takefumi, Kikuchi, Masami, Sato, Yuki, Togawa, Ryuichi, Tanino, Mishie, Tanaka, Shinya, Kadomatsu, Kenji, Munakata, Mitsuru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5582267/
https://www.ncbi.nlm.nih.gov/pubmed/28811360
http://dx.doi.org/10.14814/phy2.13383
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author Misa, Kenichi
Tanino, Yoshinori
Wang, Xintao
Nikaido, Takefumi
Kikuchi, Masami
Sato, Yuki
Togawa, Ryuichi
Tanino, Mishie
Tanaka, Shinya
Kadomatsu, Kenji
Munakata, Mitsuru
author_facet Misa, Kenichi
Tanino, Yoshinori
Wang, Xintao
Nikaido, Takefumi
Kikuchi, Masami
Sato, Yuki
Togawa, Ryuichi
Tanino, Mishie
Tanaka, Shinya
Kadomatsu, Kenji
Munakata, Mitsuru
author_sort Misa, Kenichi
collection PubMed
description Midkine is a low‐molecular‐weight heparin‐binding protein that is strongly expressed mainly in the midgestation period and has various physiological activities such as in development and cell migration. Midkine has been reported to be strongly expressed in cancer cells and in inflammation and repair processes, and to be involved in the pathogenesis of various diseases. However, its role in the lung is poorly understood. In this study, we analyzed the clinical characteristics of idiopathic pulmonary fibrosis patients in relation to midkine expression and used a mouse bleomycin‐induced pulmonary fibrosis model to investigate the role of midkine in pulmonary fibrosis. In the idiopathic pulmonary fibrosis patients, the serum midkine level was significantly higher than in healthy subjects, and midkine levels in the serum and bronchoalveolar lavage (BAL) fluid correlated positively with the percentage of inflammatory cells in the BAL fluid. In wild‐type mice, intratracheal bleomycin administration increased midkine expression in lung tissue. Additionally, compared with wild‐type mice, midkine‐deficient mice showed low expression of both collagen and α‐smooth muscle actin, as well as a low value for the pathological lung fibrosis score after bleomycin administration. Furthermore, the total cell count and lymphocyte percentage in the BAL fluid, as well as TNF‐α and transforming growth factor‐β expression in lung tissue, were significantly lower in the midkine‐deficient mice compared with wild‐type mice. These results suggest that midkine is involved in the development of pulmonary fibrosis by regulating inflammatory cell migration into the lung, and TNF‐α and transforming growth factor‐β expression.
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spelling pubmed-55822672017-09-06 Involvement of midkine in the development of pulmonary fibrosis Misa, Kenichi Tanino, Yoshinori Wang, Xintao Nikaido, Takefumi Kikuchi, Masami Sato, Yuki Togawa, Ryuichi Tanino, Mishie Tanaka, Shinya Kadomatsu, Kenji Munakata, Mitsuru Physiol Rep Original Research Midkine is a low‐molecular‐weight heparin‐binding protein that is strongly expressed mainly in the midgestation period and has various physiological activities such as in development and cell migration. Midkine has been reported to be strongly expressed in cancer cells and in inflammation and repair processes, and to be involved in the pathogenesis of various diseases. However, its role in the lung is poorly understood. In this study, we analyzed the clinical characteristics of idiopathic pulmonary fibrosis patients in relation to midkine expression and used a mouse bleomycin‐induced pulmonary fibrosis model to investigate the role of midkine in pulmonary fibrosis. In the idiopathic pulmonary fibrosis patients, the serum midkine level was significantly higher than in healthy subjects, and midkine levels in the serum and bronchoalveolar lavage (BAL) fluid correlated positively with the percentage of inflammatory cells in the BAL fluid. In wild‐type mice, intratracheal bleomycin administration increased midkine expression in lung tissue. Additionally, compared with wild‐type mice, midkine‐deficient mice showed low expression of both collagen and α‐smooth muscle actin, as well as a low value for the pathological lung fibrosis score after bleomycin administration. Furthermore, the total cell count and lymphocyte percentage in the BAL fluid, as well as TNF‐α and transforming growth factor‐β expression in lung tissue, were significantly lower in the midkine‐deficient mice compared with wild‐type mice. These results suggest that midkine is involved in the development of pulmonary fibrosis by regulating inflammatory cell migration into the lung, and TNF‐α and transforming growth factor‐β expression. John Wiley and Sons Inc. 2017-08-15 /pmc/articles/PMC5582267/ /pubmed/28811360 http://dx.doi.org/10.14814/phy2.13383 Text en © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Misa, Kenichi
Tanino, Yoshinori
Wang, Xintao
Nikaido, Takefumi
Kikuchi, Masami
Sato, Yuki
Togawa, Ryuichi
Tanino, Mishie
Tanaka, Shinya
Kadomatsu, Kenji
Munakata, Mitsuru
Involvement of midkine in the development of pulmonary fibrosis
title Involvement of midkine in the development of pulmonary fibrosis
title_full Involvement of midkine in the development of pulmonary fibrosis
title_fullStr Involvement of midkine in the development of pulmonary fibrosis
title_full_unstemmed Involvement of midkine in the development of pulmonary fibrosis
title_short Involvement of midkine in the development of pulmonary fibrosis
title_sort involvement of midkine in the development of pulmonary fibrosis
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5582267/
https://www.ncbi.nlm.nih.gov/pubmed/28811360
http://dx.doi.org/10.14814/phy2.13383
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