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HIP/PAP protects against bleomycin‐induced lung injury and inflammation and subsequent fibrosis in mice
Hepatocarcinoma‐intestine‐pancreas/pancreatitis‐associated protein (HIP/PAP), a C‐type lectin, exerts anti‐oxidative, anti‐inflammatory, bactericidal, anti‐apoptotic, and mitogenic functions in several cell types and tissues. In this study, we explored the role of HIP/PAP in pulmonary fibrosis (PF)....
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299702/ https://www.ncbi.nlm.nih.gov/pubmed/32352211 http://dx.doi.org/10.1111/jcmm.15334 |
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author | Zheng, Xiaoyan Li, Qian Tian, Hong Li, Hanchao Lv, Yifei Wang, Yanhua He, Lan Huo, Yongwei Hao, Zhiming |
author_facet | Zheng, Xiaoyan Li, Qian Tian, Hong Li, Hanchao Lv, Yifei Wang, Yanhua He, Lan Huo, Yongwei Hao, Zhiming |
author_sort | Zheng, Xiaoyan |
collection | PubMed |
description | Hepatocarcinoma‐intestine‐pancreas/pancreatitis‐associated protein (HIP/PAP), a C‐type lectin, exerts anti‐oxidative, anti‐inflammatory, bactericidal, anti‐apoptotic, and mitogenic functions in several cell types and tissues. In this study, we explored the role of HIP/PAP in pulmonary fibrosis (PF). Expression of HIP/PAP and its murine counterpart, Reg3B, was markedly increased in fibrotic human and mouse lung tissues. Adenovirus‐mediated HIP/PAP expression markedly alleviated bleomycin (BLM)‐induced lung injury, inflammation, and fibrosis in mice. Adenovirus‐mediated HIP/PAP expression alleviated oxidative injury and lessened the decrease in pulmonary superoxide dismutase (SOD) activity in BLM‐treated mice, increased pulmonary SOD expression in normal mice, and HIP/PAP upregulated SOD expression in cultured human alveolar epithelial cells (A549) and human lung fibroblasts (HLF‐1). Moreover, in vitro experiments showed that HIP/PAP suppressed the growth of HLF‐1 and ameliorated the H(2)O(2)‐induced apoptosis of human alveolar epithelial cells (A549 and HPAEpiC) and human pulmonary microvascular endothelial cells (HPMVEC). In HLF‐1, A549, HPAEpiC, and HPMVEC cells, HIP/PAP did not affect the basal levels, but alleviated the TGF‐β1‐induced down‐regulation of the epithelial/endothelial markers E‐cadherin and vE‐cadherin and the over‐expression of mesenchymal markers, such as α‐SMA and vimentin. In conclusion, HIP/PAP was found to serve as a potent protective factor in lung injury, inflammation, and fibrosis by attenuating oxidative injury, promoting the regeneration of alveolar epithelial cells, and antagonizing the pro‐fibrotic actions of the TGF‐β1/Smad signaling pathway. |
format | Online Article Text |
id | pubmed-7299702 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-72997022020-06-18 HIP/PAP protects against bleomycin‐induced lung injury and inflammation and subsequent fibrosis in mice Zheng, Xiaoyan Li, Qian Tian, Hong Li, Hanchao Lv, Yifei Wang, Yanhua He, Lan Huo, Yongwei Hao, Zhiming J Cell Mol Med Original Articles Hepatocarcinoma‐intestine‐pancreas/pancreatitis‐associated protein (HIP/PAP), a C‐type lectin, exerts anti‐oxidative, anti‐inflammatory, bactericidal, anti‐apoptotic, and mitogenic functions in several cell types and tissues. In this study, we explored the role of HIP/PAP in pulmonary fibrosis (PF). Expression of HIP/PAP and its murine counterpart, Reg3B, was markedly increased in fibrotic human and mouse lung tissues. Adenovirus‐mediated HIP/PAP expression markedly alleviated bleomycin (BLM)‐induced lung injury, inflammation, and fibrosis in mice. Adenovirus‐mediated HIP/PAP expression alleviated oxidative injury and lessened the decrease in pulmonary superoxide dismutase (SOD) activity in BLM‐treated mice, increased pulmonary SOD expression in normal mice, and HIP/PAP upregulated SOD expression in cultured human alveolar epithelial cells (A549) and human lung fibroblasts (HLF‐1). Moreover, in vitro experiments showed that HIP/PAP suppressed the growth of HLF‐1 and ameliorated the H(2)O(2)‐induced apoptosis of human alveolar epithelial cells (A549 and HPAEpiC) and human pulmonary microvascular endothelial cells (HPMVEC). In HLF‐1, A549, HPAEpiC, and HPMVEC cells, HIP/PAP did not affect the basal levels, but alleviated the TGF‐β1‐induced down‐regulation of the epithelial/endothelial markers E‐cadherin and vE‐cadherin and the over‐expression of mesenchymal markers, such as α‐SMA and vimentin. In conclusion, HIP/PAP was found to serve as a potent protective factor in lung injury, inflammation, and fibrosis by attenuating oxidative injury, promoting the regeneration of alveolar epithelial cells, and antagonizing the pro‐fibrotic actions of the TGF‐β1/Smad signaling pathway. John Wiley and Sons Inc. 2020-04-30 2020-06 /pmc/articles/PMC7299702/ /pubmed/32352211 http://dx.doi.org/10.1111/jcmm.15334 Text en © 2020 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the 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 Articles Zheng, Xiaoyan Li, Qian Tian, Hong Li, Hanchao Lv, Yifei Wang, Yanhua He, Lan Huo, Yongwei Hao, Zhiming HIP/PAP protects against bleomycin‐induced lung injury and inflammation and subsequent fibrosis in mice |
title | HIP/PAP protects against bleomycin‐induced lung injury and inflammation and subsequent fibrosis in mice |
title_full | HIP/PAP protects against bleomycin‐induced lung injury and inflammation and subsequent fibrosis in mice |
title_fullStr | HIP/PAP protects against bleomycin‐induced lung injury and inflammation and subsequent fibrosis in mice |
title_full_unstemmed | HIP/PAP protects against bleomycin‐induced lung injury and inflammation and subsequent fibrosis in mice |
title_short | HIP/PAP protects against bleomycin‐induced lung injury and inflammation and subsequent fibrosis in mice |
title_sort | hip/pap protects against bleomycin‐induced lung injury and inflammation and subsequent fibrosis in mice |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299702/ https://www.ncbi.nlm.nih.gov/pubmed/32352211 http://dx.doi.org/10.1111/jcmm.15334 |
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