Morphine induces fibroblast activation through up-regulation of connexin 43 expression: Implication of fibrosis in wound healing

Ping Ching Wu, Wen Li Hsu, Chun Lin Chen, Chen Fuh Lam, Yaw Bin Huang, Chien Chi Huang, Ming Hong Lin, Ming Wei Lin

研究成果: Article

摘要

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.

原文English
頁(從 - 到)875-882
頁數8
期刊International Journal of Medical Sciences
15
發行號9
DOIs
出版狀態Published - 2018 六月 4

指紋

Connexin 43
Wound Healing
Morphine
Fibrosis
Up-Regulation
Fibroblasts
Myofibroblasts
Transforming Growth Factors
Morphine Dependence
Focal Adhesions
Fibronectins
Smooth Muscle
Actins
Pain

All Science Journal Classification (ASJC) codes

  • Medicine(all)

引用此文

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. 於: International Journal of Medical Sciences. 2018 ; 卷 15, 編號 9. 頁 875-882.
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abstract = "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.",
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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.

於: International Journal of Medical Sciences, 卷 15, 編號 9, 04.06.2018, p. 875-882.

研究成果: Article

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AU - Lin, Ming Hong

AU - Lin, Ming Wei

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