| First Author | Siebert N | Year | 2011 |
| Journal | Lab Invest | Volume | 91 |
| Issue | 12 | Pages | 1753-65 |
| PubMed ID | 21894148 | Mgi Jnum | J:180037 |
| Mgi Id | MGI:5305015 | Doi | 10.1038/labinvest.2011.125 |
| Citation | Siebert N, et al. (2011) Erythropoietin improves skin wound healing and activates the TGF-beta signaling pathway. Lab Invest 91(12):1753-65 |
| abstractText | 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)-beta 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-beta1 and of alpha-smooth muscle actin (alpha-SMA) compared with non-wounded skin. EPO treatment accelerated wound epithelialization and induced mRNA expression of TGF-beta1 and alpha-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-beta using a neutralizing anti-TGF-beta antibody attenuated EPO-induced acceleration of wound epithelialization in vivo and markedly reversed EPO effects on mRNA expression of TGF-beta1 and alpha-SMA. In conclusion, EPO caused activation of the Smad-dependent TGF-beta signaling pathway, enhanced differentiation of myofibroblasts, and accelerated skin wound closure. |
