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Silencing of Carbohydrate Sulfotransferase 15 Hinders Murine Pulmonary Fibrosis Development
Pulmonary fibrosis is a progressive lung disorder characterized by interstitial fibrosis, for which no effective treatments are available. Chondroitin sulfate proteoglycan (CSPG) has been shown to be a mediator, but the specific component of glycosaminoglycan chains of CSPG has not been explored. We...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society of Gene & Cell Therapy
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363499/ https://www.ncbi.nlm.nih.gov/pubmed/28325283 http://dx.doi.org/10.1016/j.omtn.2016.12.008 |
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author | Kai, Yoshiro Tomoda, Koichi Yoneyama, Hiroyuki Kitabatake, Masahiro Nakamura, Atsuhiro Ito, Toshihiro Yoshikawa, Masanori Kimura, Hiroshi |
author_facet | Kai, Yoshiro Tomoda, Koichi Yoneyama, Hiroyuki Kitabatake, Masahiro Nakamura, Atsuhiro Ito, Toshihiro Yoshikawa, Masanori Kimura, Hiroshi |
author_sort | Kai, Yoshiro |
collection | PubMed |
description | Pulmonary fibrosis is a progressive lung disorder characterized by interstitial fibrosis, for which no effective treatments are available. Chondroitin sulfate proteoglycan (CSPG) has been shown to be a mediator, but the specific component of glycosaminoglycan chains of CSPG has not been explored. We show that chondroitin sulfate E-type (CS-E) is involved in fibrogenesis. Small interfering RNA (siRNA) targeting carbohydrate sulfotransferase 15 (CHST15) was designed to inhibit CHST15 mRNA and its product, CS-E. CS-E augments cell contraction and CHST15 siRNA inhibits collagen production. We found that bleomycin treatment increased CHST15 expression in interstitial fibroblasts at day 14. CHST15 siRNA was injected intranasally on days 1, 4, 8, and 11, and CHST15 mRNA was significantly suppressed by day 14. CHST15 siRNA reduced lung CSPG and the grade of fibrosis. CHST15 siRNA repressed the activation of fibroblasts, as evidenced by suppressed expression of α smooth muscle actin (αSMA), connective tissue growth factor (CTGF), lysyl oxidase like 2 (LOXL2), and CC-chemokine ligand 2 (CCL2)/monocyte chemoattractant protein-1 (MCP-1). Inflammatory infiltrates in the bronchoalveolar lavage fluid (BALF) and interstitium were diminished by CHST15 siRNA. These results indicate a pivotal role for CHST15 in fibroblast-mediated lung fibrosis and suggest a possible new therapeutic role for CHST15 siRNA in pulmonary fibrosis. |
format | Online Article Text |
id | pubmed-5363499 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
spelling | pubmed-53634992017-03-24 Silencing of Carbohydrate Sulfotransferase 15 Hinders Murine Pulmonary Fibrosis Development Kai, Yoshiro Tomoda, Koichi Yoneyama, Hiroyuki Kitabatake, Masahiro Nakamura, Atsuhiro Ito, Toshihiro Yoshikawa, Masanori Kimura, Hiroshi Mol Ther Nucleic Acids Original Article Pulmonary fibrosis is a progressive lung disorder characterized by interstitial fibrosis, for which no effective treatments are available. Chondroitin sulfate proteoglycan (CSPG) has been shown to be a mediator, but the specific component of glycosaminoglycan chains of CSPG has not been explored. We show that chondroitin sulfate E-type (CS-E) is involved in fibrogenesis. Small interfering RNA (siRNA) targeting carbohydrate sulfotransferase 15 (CHST15) was designed to inhibit CHST15 mRNA and its product, CS-E. CS-E augments cell contraction and CHST15 siRNA inhibits collagen production. We found that bleomycin treatment increased CHST15 expression in interstitial fibroblasts at day 14. CHST15 siRNA was injected intranasally on days 1, 4, 8, and 11, and CHST15 mRNA was significantly suppressed by day 14. CHST15 siRNA reduced lung CSPG and the grade of fibrosis. CHST15 siRNA repressed the activation of fibroblasts, as evidenced by suppressed expression of α smooth muscle actin (αSMA), connective tissue growth factor (CTGF), lysyl oxidase like 2 (LOXL2), and CC-chemokine ligand 2 (CCL2)/monocyte chemoattractant protein-1 (MCP-1). Inflammatory infiltrates in the bronchoalveolar lavage fluid (BALF) and interstitium were diminished by CHST15 siRNA. These results indicate a pivotal role for CHST15 in fibroblast-mediated lung fibrosis and suggest a possible new therapeutic role for CHST15 siRNA in pulmonary fibrosis. American Society of Gene & Cell Therapy 2017-03-17 2016-12-31 /pmc/articles/PMC5363499/ /pubmed/28325283 http://dx.doi.org/10.1016/j.omtn.2016.12.008 Text en © 2016 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Kai, Yoshiro Tomoda, Koichi Yoneyama, Hiroyuki Kitabatake, Masahiro Nakamura, Atsuhiro Ito, Toshihiro Yoshikawa, Masanori Kimura, Hiroshi Silencing of Carbohydrate Sulfotransferase 15 Hinders Murine Pulmonary Fibrosis Development |
title | Silencing of Carbohydrate Sulfotransferase 15 Hinders Murine Pulmonary Fibrosis Development |
title_full | Silencing of Carbohydrate Sulfotransferase 15 Hinders Murine Pulmonary Fibrosis Development |
title_fullStr | Silencing of Carbohydrate Sulfotransferase 15 Hinders Murine Pulmonary Fibrosis Development |
title_full_unstemmed | Silencing of Carbohydrate Sulfotransferase 15 Hinders Murine Pulmonary Fibrosis Development |
title_short | Silencing of Carbohydrate Sulfotransferase 15 Hinders Murine Pulmonary Fibrosis Development |
title_sort | silencing of carbohydrate sulfotransferase 15 hinders murine pulmonary fibrosis development |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363499/ https://www.ncbi.nlm.nih.gov/pubmed/28325283 http://dx.doi.org/10.1016/j.omtn.2016.12.008 |
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