Hübner G, Hu Q, Smola H, Werner S
Max-Planck-Institut für Biochemie, Martinsried, Germany.
Dev Biol. 1996 Feb 1;173(2):490-8. doi: 10.1006/dbio.1996.0042.
Activins are members of the transforming growth factor beta (TGF beta) superfamily, which comprises a growing group of dimeric proteins. TGF beta and several other members of this superfamily are known to play an important role in wound healing. However, expression of activin during wound healing has not been demonstrated so far. In this study we have analyzed the expression pattern of activin and activin receptors in normal and wounded skin. We found a large induction of activin A and a minor induction of activin B mRNA expression 1 day after skin injury and high expression levels of activin A and B were found within the first 7 days after wounding. At 13 days after injury, expression of activin A mRNA had returned to the basal level, whereas high levels of activin B persisted. In situ hybridization studies revealed expression of activin A in the granulation tissue below the wound and activin B in the hyperproliferative epithelium at the wound edge and in the migrating epithelial tongue. All known types of activin receptors as well as the activin binding protein follistatin were expressed in normal and wounded skin. However, no significant induction of receptor gene expression was seen during the repair process. The distribution of activins and activin receptors in the wound suggests multiple autocrine and paracrine activities of the ligands during wound healing. Our data provide evidence for a novel function of activin and indicate that--besides TGF beta s themselves--other members of this superfamily might also play an important role in tissue repair.
激活素是转化生长因子β（TGFβ）超家族的成员，该超家族由越来越多的二聚体蛋白组成。已知TGFβ和该超家族的其他几个成员在伤口愈合中起重要作用。然而，迄今为止尚未证实激活素在伤口愈合过程中的表达情况。在本研究中，我们分析了正常皮肤和伤口皮肤中激活素及其受体的表达模式。我们发现皮肤损伤后1天，激活素A大量诱导表达，激活素B mRNA有少量诱导表达，并且在伤口后的前7天内发现激活素A和B的表达水平很高。损伤后13天，激活素A mRNA的表达已恢复到基础水平，而激活素B仍持续高水平表达。原位杂交研究显示，激活素A在伤口下方的肉芽组织中表达，激活素B在伤口边缘的过度增殖上皮以及迁移的上皮舌中表达。所有已知类型的激活素受体以及激活素结合蛋白卵泡抑素在正常皮肤和伤口皮肤中均有表达。然而，在修复过程中未观察到受体基因表达的显著诱导。激活素及其受体在伤口中的分布表明，在伤口愈合过程中配体具有多种自分泌和旁分泌活性。我们的数据为激活素的新功能提供了证据，并表明——除了TGFβ本身——该超家族的其他成员也可能在组织修复中起重要作用。
