title: Erythropoietin improves skin wound healing and activates the TGF-β signaling pathway.
abstract: We could recently report that erythropoietin (EPO) accelerates skin wound healing in mice. Now, we provide insight into the molecular mechanisms of this non-hematopoietic property of EPO analyzing the transforming growth factor (TGF)-β signaling pathway. EPO receptor was found expressed in both non-wounded and wounded skin tissue as well as in fibroblasts and keratinocytes. In saline-treated control animals, wounds exhibited a significant upregulation of TGF-β1 and of α-smooth muscle actin (α-SMA) compared with non-wounded skin. EPO treatment accelerated wound epithelialization and induced mRNA expression of TGF-β1 and α-SMA. In addition, EPO significantly enhanced phosphorylation of Smad2 and Smad3 in fibroblasts and also elevated phosphorylation of Smad3 in wound tissue. Blockade of TGF-β using a neutralizing anti-TGF-β antibody attenuated EPO-induced acceleration of wound epithelialization in vivo and markedly reversed EPO effects on mRNA expression of TGF-β1 and α-SMA. In conclusion, EPO caused activation of the Smad-dependent TGF-β signaling pathway, enhanced differentiation of myofibroblasts, and accelerated skin wound closure.
authors: Institute for Experimental Surgery, University of Rostock, Rostock, Germany.
authors: Nikolai
authors: N
authors: Siebert
authors: Weiguo
authors: W
authors: Xu
authors: Eberhard
authors: E
authors: Grambow
authors: Dietmar
authors: D
authors: Zechner
authors: Brigitte
authors: B
authors: Vollmar
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D054443:Cell Migration Assays; D004921:Erythropoietin / Q000378:metabolism* / Q000627:therapeutic use; D005347:Fibroblasts / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014945:Wound Healing
chemical_list: C558396:Acta2 protein, mouse; D000199:Actins; D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; C508961:Tgfb1 protein, mouse; D053773:Transforming Growth Factor beta1; D004921:Erythropoietin