Schmid P, Cox D, Bilbe G, McMaster G, Morrison C, Stähelin H, Lüscher N, Seiler W
Ciba-Geigy Ltd., Pharma Division, Biotechnology, Basel, Switzerland.
J Pathol. 1993 Nov;171(3):191-7. doi: 10.1002/path.1711710307.
Exogenously applied transforming growth factor-beta (TGF-beta) isoforms enhance wound healing processes in animal models; however, little is known about the expression of endogenous TGF-beta s and TGF-beta receptors in intact human skin or during wound healing. The present study has revealed several unexpected findings by means of in situ hybridization and immunohistology techniques. In humans, TGF-beta 3 is constitutively expressed in the epidermis of intact skin and in that of acute and chronic wounds--a pattern of expression closely mirrored by the TGF-beta type II receptor. Although not detected in intact skin, TGF-beta 1 mRNA expression was observed in the regenerating epidermis of acute (thermal) wounds but was not found in chronic decubital (pressure) wounds. TGF-beta 2 mRNA expression was not detected in the epidermis of any human skin or wound biopsies. From these findings we suggest that constitutive expression of TGF-beta 3 is important for maintenance of epidermal differentiation and that an induction of TGF-beta 1 expression is essential for re-epithelialization of human skin wounds. Lack of TGF-beta 1 expression in chronic pressure wounds may be associated with their protracted healing tendencies.
外源性应用的转化生长因子-β(TGF-β)亚型可促进动物模型中的伤口愈合过程;然而,对于内源性TGF-βs和TGF-β受体在完整人类皮肤或伤口愈合过程中的表达情况却知之甚少。本研究通过原位杂交和免疫组织学技术揭示了几个意外的发现。在人类中,TGF-β3在完整皮肤的表皮以及急性和慢性伤口的表皮中组成性表达——这种表达模式与II型TGF-β受体密切相似。虽然在完整皮肤中未检测到,但在急性(热)伤口的再生表皮中观察到TGF-β1 mRNA表达,而在慢性褥疮(压力)伤口中未发现。在任何人类皮肤或伤口活检的表皮中均未检测到TGF-β2 mRNA表达。基于这些发现,我们认为TGF-β3的组成性表达对于维持表皮分化很重要,而TGF-β1表达的诱导对于人类皮肤伤口的重新上皮化至关重要。慢性压力伤口中TGF-β1表达的缺乏可能与其愈合延迟的倾向有关。