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Morphine Induces Fibroblast Activation through Up-regulation of Connexin 43 Expression: Implication of Fibrosis in Wound Healing
Morphine is the most effective drugs for attenuating various types of severe pain, but morphine abuse carries a high risk of systemic fibrosis. Our previous have indicated that systemic administration of morphine hinders angiogenesis and delays wound healing. Here we have explained the pathological...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036091/ https://www.ncbi.nlm.nih.gov/pubmed/30008599 http://dx.doi.org/10.7150/ijms.23074 |
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author | Wu, Ping-Ching Hsu, Wen-Li Chen, Chun-Lin Lam, Chen-Fuh Huang, Yaw-Bin Huang, Chien-Chi Lin, Ming-Hong Lin, Ming-Wei |
author_facet | Wu, Ping-Ching Hsu, Wen-Li Chen, Chun-Lin Lam, Chen-Fuh Huang, Yaw-Bin Huang, Chien-Chi Lin, Ming-Hong Lin, Ming-Wei |
author_sort | Wu, Ping-Ching |
collection | PubMed |
description | Morphine is the most effective drugs for attenuating various types of severe pain, but morphine abuse carries a high risk of systemic fibrosis. Our previous have indicated that systemic administration of morphine hinders angiogenesis and delays wound healing. Here we have explained the pathological mechanism underlying the effect of morphine on wound healing. To determine how morphine affects wound healing, we first created a wound in mice treated them with a combination of a low doses (5 mg/kg/day) and high doses (20 or 30 mg/kg/day) of morphine. An In vivo study revealed that high-dose morphine-induced abnormal myofibroblasts persist after the end of wound healing because of connexin 43 (Cx43) upregulation. High-dose morphine-induced Cx43 increased the expression levels of focal adhesion molecules, namely fibronectin and alpha-smooth muscle actin (α-SMA) through the activation of transforming growth factor (TGF)-β1 signaling. In addition, we found that Cx43 contributed to TGF-βRII/ Smad2/3 signaling for regulating the differentiation of fibroblasts into myofibroblasts during high-dose morphine exposure. In conclusion, the abnormal regulation of Cx43 by morphine may induce systemic fibrosis because of abnormal myofibroblast function. |
format | Online Article Text |
id | pubmed-6036091 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-60360912018-07-15 Morphine Induces Fibroblast Activation through Up-regulation of Connexin 43 Expression: Implication of Fibrosis in Wound Healing Wu, Ping-Ching Hsu, Wen-Li Chen, Chun-Lin Lam, Chen-Fuh Huang, Yaw-Bin Huang, Chien-Chi Lin, Ming-Hong Lin, Ming-Wei Int J Med Sci Research Paper Morphine is the most effective drugs for attenuating various types of severe pain, but morphine abuse carries a high risk of systemic fibrosis. Our previous have indicated that systemic administration of morphine hinders angiogenesis and delays wound healing. Here we have explained the pathological mechanism underlying the effect of morphine on wound healing. To determine how morphine affects wound healing, we first created a wound in mice treated them with a combination of a low doses (5 mg/kg/day) and high doses (20 or 30 mg/kg/day) of morphine. An In vivo study revealed that high-dose morphine-induced abnormal myofibroblasts persist after the end of wound healing because of connexin 43 (Cx43) upregulation. High-dose morphine-induced Cx43 increased the expression levels of focal adhesion molecules, namely fibronectin and alpha-smooth muscle actin (α-SMA) through the activation of transforming growth factor (TGF)-β1 signaling. In addition, we found that Cx43 contributed to TGF-βRII/ Smad2/3 signaling for regulating the differentiation of fibroblasts into myofibroblasts during high-dose morphine exposure. In conclusion, the abnormal regulation of Cx43 by morphine may induce systemic fibrosis because of abnormal myofibroblast function. Ivyspring International Publisher 2018-06-04 /pmc/articles/PMC6036091/ /pubmed/30008599 http://dx.doi.org/10.7150/ijms.23074 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Wu, Ping-Ching Hsu, Wen-Li Chen, Chun-Lin Lam, Chen-Fuh Huang, Yaw-Bin Huang, Chien-Chi Lin, Ming-Hong Lin, Ming-Wei Morphine Induces Fibroblast Activation through Up-regulation of Connexin 43 Expression: Implication of Fibrosis in Wound Healing |
title | Morphine Induces Fibroblast Activation through Up-regulation of Connexin 43 Expression: Implication of Fibrosis in Wound Healing |
title_full | Morphine Induces Fibroblast Activation through Up-regulation of Connexin 43 Expression: Implication of Fibrosis in Wound Healing |
title_fullStr | Morphine Induces Fibroblast Activation through Up-regulation of Connexin 43 Expression: Implication of Fibrosis in Wound Healing |
title_full_unstemmed | Morphine Induces Fibroblast Activation through Up-regulation of Connexin 43 Expression: Implication of Fibrosis in Wound Healing |
title_short | Morphine Induces Fibroblast Activation through Up-regulation of Connexin 43 Expression: Implication of Fibrosis in Wound Healing |
title_sort | morphine induces fibroblast activation through up-regulation of connexin 43 expression: implication of fibrosis in wound healing |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036091/ https://www.ncbi.nlm.nih.gov/pubmed/30008599 http://dx.doi.org/10.7150/ijms.23074 |
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