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Epithelial cell-derived cytokines CST3 and GDF15 as potential therapeutics for pulmonary fibrosis

While wound healing is completed, the epithelium functions to normalize the interstitial context by eliminating fibroblasts excited during matrix reconstruction. If not, tissues undergo pathologic fibrosis. Pulmonary fibrosis is a fatal and hardly curable disorder. We here tried to identify epitheli...

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Autores principales: Kim, Young-Im, Shin, Hyun-Woo, Chun, Yang-Sook, Cho, Chung-Hyun, Koh, Jaemoon, Chung, Doo Hyun, Park, Jong-Wan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938700/
https://www.ncbi.nlm.nih.gov/pubmed/29724997
http://dx.doi.org/10.1038/s41419-018-0530-0
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author Kim, Young-Im
Shin, Hyun-Woo
Chun, Yang-Sook
Cho, Chung-Hyun
Koh, Jaemoon
Chung, Doo Hyun
Park, Jong-Wan
author_facet Kim, Young-Im
Shin, Hyun-Woo
Chun, Yang-Sook
Cho, Chung-Hyun
Koh, Jaemoon
Chung, Doo Hyun
Park, Jong-Wan
author_sort Kim, Young-Im
collection PubMed
description While wound healing is completed, the epithelium functions to normalize the interstitial context by eliminating fibroblasts excited during matrix reconstruction. If not, tissues undergo pathologic fibrosis. Pulmonary fibrosis is a fatal and hardly curable disorder. We here tried to identify epithelium-derived cytokines capable of ameliorating pulmonary fibrosis. Human lung fibroblasts were inactivated in epithelial cell-conditioned media. Cystatin C (CST3) and growth differentiation factor 15 (GDF15) were found to be enriched in the conditioned media and to inhibit the growth and activation of lung fibroblasts by inactivating the TGF–Smad pathway. In mouse and human lungs with interstitial fibrosis, CST3 and GDF15 expressions were markedly reduced, and the restoration of these cytokines alleviated the fibrotic changes in mouse lungs. These results suggest that CST3 and GDF15 are bona fide regulators to prevent excessive proliferation and activation of fibroblasts in injured lungs. These cytokines could be potential therapeutics for ameliorating interstitial lung fibrosis.
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spelling pubmed-59387002018-05-09 Epithelial cell-derived cytokines CST3 and GDF15 as potential therapeutics for pulmonary fibrosis Kim, Young-Im Shin, Hyun-Woo Chun, Yang-Sook Cho, Chung-Hyun Koh, Jaemoon Chung, Doo Hyun Park, Jong-Wan Cell Death Dis Article While wound healing is completed, the epithelium functions to normalize the interstitial context by eliminating fibroblasts excited during matrix reconstruction. If not, tissues undergo pathologic fibrosis. Pulmonary fibrosis is a fatal and hardly curable disorder. We here tried to identify epithelium-derived cytokines capable of ameliorating pulmonary fibrosis. Human lung fibroblasts were inactivated in epithelial cell-conditioned media. Cystatin C (CST3) and growth differentiation factor 15 (GDF15) were found to be enriched in the conditioned media and to inhibit the growth and activation of lung fibroblasts by inactivating the TGF–Smad pathway. In mouse and human lungs with interstitial fibrosis, CST3 and GDF15 expressions were markedly reduced, and the restoration of these cytokines alleviated the fibrotic changes in mouse lungs. These results suggest that CST3 and GDF15 are bona fide regulators to prevent excessive proliferation and activation of fibroblasts in injured lungs. These cytokines could be potential therapeutics for ameliorating interstitial lung fibrosis. Nature Publishing Group UK 2018-05-03 /pmc/articles/PMC5938700/ /pubmed/29724997 http://dx.doi.org/10.1038/s41419-018-0530-0 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kim, Young-Im
Shin, Hyun-Woo
Chun, Yang-Sook
Cho, Chung-Hyun
Koh, Jaemoon
Chung, Doo Hyun
Park, Jong-Wan
Epithelial cell-derived cytokines CST3 and GDF15 as potential therapeutics for pulmonary fibrosis
title Epithelial cell-derived cytokines CST3 and GDF15 as potential therapeutics for pulmonary fibrosis
title_full Epithelial cell-derived cytokines CST3 and GDF15 as potential therapeutics for pulmonary fibrosis
title_fullStr Epithelial cell-derived cytokines CST3 and GDF15 as potential therapeutics for pulmonary fibrosis
title_full_unstemmed Epithelial cell-derived cytokines CST3 and GDF15 as potential therapeutics for pulmonary fibrosis
title_short Epithelial cell-derived cytokines CST3 and GDF15 as potential therapeutics for pulmonary fibrosis
title_sort epithelial cell-derived cytokines cst3 and gdf15 as potential therapeutics for pulmonary fibrosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938700/
https://www.ncbi.nlm.nih.gov/pubmed/29724997
http://dx.doi.org/10.1038/s41419-018-0530-0
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