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Morphine induces endothelial‐to‐mesenchymal transition by up‐regulation of gap junction protein Connexin 43 expression during wound healing
Author(s) -
Lin MingWei,
Chiou ChiuanShiou,
Lam ChenFuh,
Huang YawBin,
Huang ChienChi,
Liu YenChin,
Tsai YuChuan,
Wu PingChing
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.875.4
Subject(s) - wound healing , fibronectin , myofibroblast , angiogenesis , mesenchymal stem cell , microbiology and biotechnology , connexin , fibroblast , progenitor cell , endothelial stem cell , cancer research , fibrosis , chemistry , medicine , gap junction , immunology , biology , pathology , stem cell , extracellular matrix , in vitro , intracellular , biochemistry
Morphine is commonly used in controlling of severe wound pain, although pulmonary fibrosis has been found in patients of morphine abuse. Our previous studies indicated that morphine impaired angiogenesis and delayed wound healing. Recent studies have also demonstrated that up‐regulation of gap junction channels, connexin43 (Cx43), delayedthe wound healing by alteration of fibroblast proliferation and promoted endothelial–mesenchymal transition/transformation(EMT) after endothelial injury in vivo. During EMT, endothelial cells differentiate into α‐SMA‐expressing myofibroblasts, and result in endothelial dysfunction. Here, we sought to investigate whether morphine contributed to differentiation of endothelial cells and activation of fibroblasts through alteration of Cx43 expression, and thereby delayed wound healing. In incisional wound tissue of mice, we found that morphine up‐regulated Cx43, α‐SMA and fibronectin. Morphine not only elevated Cx43 protein level in human endothelial cells, endothelial progenitor cells, and fibroblasts, but also promoted these cells differentiation into α‐SMA‐expressing cells. Knock‐down of Cx43 by siRNA impaired α‐SMA and fibronectin expression in human fibroblasts. Therefore, we concluded that morphine may induce α‐SMA expression contributing to modulate endothelial cells and fibroblasts function through Cx43 during wound repair. Moreover, abnormal regulation of Cx43 by morphine may induce tissue fibrosis.