23 February 2019
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Int J Med Sci 2018; 15(9):875-882. doi:10.7150/ijms.23074
Morphine Induces Fibroblast Activation through Up-regulation of Connexin 43 Expression: Implication of Fibrosis in Wound Healing
1. Department of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan
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.
Keywords: Morphine, Wound Healing, Fibrosis, Cx43
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How to cite this article:
Wu PC, Hsu WL, Chen CL, Lam CF, Huang YB, Huang CC, Lin MH, Lin MW. Morphine Induces Fibroblast Activation through Up-regulation of Connexin 43 Expression: Implication of Fibrosis in Wound Healing. Int J Med Sci 2018; 15(9):875-882. doi:10.7150/ijms.23074. Available from http://www.medsci.org/v15p0875.htm