Journal of Tissue Engineering and Reconstructive Surgery ›› 2018, Vol. 14 ›› Issue (4): 188-193.doi: 10.3969/j.issn.1673-0364.2018.04.003

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The Inhibition Effect of AMPK Agonist on the Formation of Keloid

CAI Haifeng,YIN Jiafei,WANG Chen,ZHOU Renpeng,WANG Zejian,WANG Danru   

  1. Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine;Shanghai Jiaotong University School of Pharmacy
  • Received:2018-05-18 Revised:2018-08-16 Published:2020-07-23
  • Contact: 国家自然科学基金面上项目(项目编号:81671923)

Abstract: Objective To explore the interference effect of AMPK agonist on the formation of keloid, and to provide new ideas for the clinical treatment of keloid. Methods In vitro culture conditions of skin fibroblasts phenotype to the keloid phenotype transformation were established by hypoxia and different concentrations (0, 2.5, 5, 10, 20 ng/mL) of TGF-β1, and confirmed by cell morphology and Western blot. Subsequently, different doses (2.5, 5, 10, 20 μmol) of AMPK agonist (A769662) were added to observe its effect on the phenotypic transformation of skin fibroblast to keloid. The reserve effect was confirmed by cell morphology, the expression of related markers (E-cadherin, Vimentin, ACTA2, Collagen I , IRS-1, Glut4, p-H2AX/H2AX2, NANOG, OCT4) detected by Western blot and the expression of IL-6 and VEGF detected by ELISA. Results The spindle shape of skin fibroblasts lost under hypoxia and inflammation induction by TGF-β1. In the process of increasing TGF-β1 concentration to 10 ng/mL, TGF-β1 stimulated the transformation of phenotype of fibroblasts into keloid associated phenotype. As the concentration continued to increase, the effects were arrested and slightly reversed. At the same concentration (10 ng/mL) induced by TGF-β1, the process of cell transformation was gradually intervened with the increasing dose of AMPK agonists added. Under hypoxia condition, the expression of VEGF and IL-6 in skin fibroblasts was significantly increased. Under the induction of TGF-β1, the expression of VEGF and IL-6 was further increased. And with the addition of AMPK agonists, the expression of VEGF and IL-6 was progressively reduced. Conclusion AMPK agonists can inhibit the transformation of fibroblast to keloid associated phenotype induced by hypoxia and inflammation.

Key words: Keloid, Skin fibroblasts, Myofibroblastic transformation, AMPK agonist

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