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Effect of SIS3 on Extracellular Matrix Remodeling and Repair in a Lipopolysaccharide-Induced ARDS Rat Model

The remodeling of the extracellular matrix (ECM) in the parenchyma plays an important role in the development of acute respiratory distress syndrome (ARDS), a disease characterized by lung injury. Although it is clear that TGF-β1 can modulate the expression of the extracellular matrix (ECM) through...

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Autores principales: Liang, Qiong, Lin, Qiqing, Li, Yueyong, Luo, Weigui, Huang, Xia, Jiang, Yujie, Qin, Chunyan, Nong, Jin, Chen, Xiang, Sooranna, Suren Rao, Pinhu, Liao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714568/
https://www.ncbi.nlm.nih.gov/pubmed/33294466
http://dx.doi.org/10.1155/2020/6644687
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author Liang, Qiong
Lin, Qiqing
Li, Yueyong
Luo, Weigui
Huang, Xia
Jiang, Yujie
Qin, Chunyan
Nong, Jin
Chen, Xiang
Sooranna, Suren Rao
Pinhu, Liao
author_facet Liang, Qiong
Lin, Qiqing
Li, Yueyong
Luo, Weigui
Huang, Xia
Jiang, Yujie
Qin, Chunyan
Nong, Jin
Chen, Xiang
Sooranna, Suren Rao
Pinhu, Liao
author_sort Liang, Qiong
collection PubMed
description The remodeling of the extracellular matrix (ECM) in the parenchyma plays an important role in the development of acute respiratory distress syndrome (ARDS), a disease characterized by lung injury. Although it is clear that TGF-β1 can modulate the expression of the extracellular matrix (ECM) through intracellular signaling molecules such as Smad3, its role as a therapeutic target against ARDS remains unknown. In this study, a rat model was established to mimic ARDS via intratracheal instillation of lipopolysaccharide (LPS). A selective inhibitor of Smad3 (SIS3) was intraperitoneally injected into the disease model, while phosphate-buffered saline (PBS) was used in the control group. Animal tissues were then evaluated using histological analysis, immunohistochemistry, RT-qPCR, ELISA, and western blotting. LPS was found to stimulate the expression of RAGE, TGF-β1, MMP2, and MMP9 in the rat model. Moreover, treatment with SIS3 was observed to reverse the expression of these molecules. In addition, pretreatment with SIS3 was shown to partially inhibit the phosphorylation of Smad3 and alleviate symptoms including lung injury and pulmonary edema. These findings indicate that SIS3, or the blocking of TGF-β/Smad3 pathways, could influence remodeling of the ECM and this may serve as a therapeutic strategy against ARDS.
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spelling pubmed-77145682020-12-07 Effect of SIS3 on Extracellular Matrix Remodeling and Repair in a Lipopolysaccharide-Induced ARDS Rat Model Liang, Qiong Lin, Qiqing Li, Yueyong Luo, Weigui Huang, Xia Jiang, Yujie Qin, Chunyan Nong, Jin Chen, Xiang Sooranna, Suren Rao Pinhu, Liao J Immunol Res Research Article The remodeling of the extracellular matrix (ECM) in the parenchyma plays an important role in the development of acute respiratory distress syndrome (ARDS), a disease characterized by lung injury. Although it is clear that TGF-β1 can modulate the expression of the extracellular matrix (ECM) through intracellular signaling molecules such as Smad3, its role as a therapeutic target against ARDS remains unknown. In this study, a rat model was established to mimic ARDS via intratracheal instillation of lipopolysaccharide (LPS). A selective inhibitor of Smad3 (SIS3) was intraperitoneally injected into the disease model, while phosphate-buffered saline (PBS) was used in the control group. Animal tissues were then evaluated using histological analysis, immunohistochemistry, RT-qPCR, ELISA, and western blotting. LPS was found to stimulate the expression of RAGE, TGF-β1, MMP2, and MMP9 in the rat model. Moreover, treatment with SIS3 was observed to reverse the expression of these molecules. In addition, pretreatment with SIS3 was shown to partially inhibit the phosphorylation of Smad3 and alleviate symptoms including lung injury and pulmonary edema. These findings indicate that SIS3, or the blocking of TGF-β/Smad3 pathways, could influence remodeling of the ECM and this may serve as a therapeutic strategy against ARDS. Hindawi 2020-11-25 /pmc/articles/PMC7714568/ /pubmed/33294466 http://dx.doi.org/10.1155/2020/6644687 Text en Copyright © 2020 Qiong Liang et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Liang, Qiong
Lin, Qiqing
Li, Yueyong
Luo, Weigui
Huang, Xia
Jiang, Yujie
Qin, Chunyan
Nong, Jin
Chen, Xiang
Sooranna, Suren Rao
Pinhu, Liao
Effect of SIS3 on Extracellular Matrix Remodeling and Repair in a Lipopolysaccharide-Induced ARDS Rat Model
title Effect of SIS3 on Extracellular Matrix Remodeling and Repair in a Lipopolysaccharide-Induced ARDS Rat Model
title_full Effect of SIS3 on Extracellular Matrix Remodeling and Repair in a Lipopolysaccharide-Induced ARDS Rat Model
title_fullStr Effect of SIS3 on Extracellular Matrix Remodeling and Repair in a Lipopolysaccharide-Induced ARDS Rat Model
title_full_unstemmed Effect of SIS3 on Extracellular Matrix Remodeling and Repair in a Lipopolysaccharide-Induced ARDS Rat Model
title_short Effect of SIS3 on Extracellular Matrix Remodeling and Repair in a Lipopolysaccharide-Induced ARDS Rat Model
title_sort effect of sis3 on extracellular matrix remodeling and repair in a lipopolysaccharide-induced ards rat model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714568/
https://www.ncbi.nlm.nih.gov/pubmed/33294466
http://dx.doi.org/10.1155/2020/6644687
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