McMullen H, Longaker M T, Cabrera R C, Sung J, Canete J, Siebert J W, Lorenz H P, Gold L I
Department of Surgery, New York University Medical Center, New York, NY 10016, USA.
Wound Repair Regen. 1995 Apr-Jun;3(2):141-56. doi: 10.1046/j.1524-475X.1995.30206.x.
To elucidate the role for transforming growth factor-beta isoforms (beta(1), -beta(2), and -beta(3)) in wound repair, we used isoform-specific antibodies to detect the spatial and temporal expression of the latent and mature/active transforming growth factor-beta isoforms by immunohistochemical localization through 21 days after excisional and incisional wounding of ovine skin. Although incisional and excisional wounds showed similar patterns of transforming growth factor-beta immunoreactivity, we found a differential temporal and spatial expression of the latent and mature transforming growth factor-beta isoforms throughout wound repair. Specifically, 1 day after wounding, there was a marked increase in transforming growth factor-beta isoforms in the epithelium adjacent to the wound, epidermal appendages, and the cells and matrix of the granulation tissue. At this time, transforming growth factor-beta(3) isoform was the most abundant. Most notably, the epidermis adjacent to the wound was intensely immunoreactive for all transforming growth factor-beta isoforms 1 day after injury. However, the migrating epithelium, derived from both the hair follicles and the wound margins, was completely devoid of immunoreactive transforming growth factor-beta until reepithelialization was complete. Within the inflammatory exudate, there was a distinct band of leukocytes that was immunoreactive for transforming growth factor-beta(2) and -beta(3) 1 day after injury and 1 day later for transforming growth factor-beta(1). Although transforming growth factor-beta(1) and -beta(2), latent transforming growth factor-beta(2), transforming growth factor-beta(3), and latent transforming growth factor-beta(3) immunostaining was present in the numerous fibroblasts and other dermal cells, latent transforming growth factor-beta(1) was only associated with the extracellular matrix. In general, immunoreactivity remained high until day 7 after wounding and slowly subsided over time. However, by day 21, immunostaining had not returned to normal and the original wound was replete with immunoreactive fibroblasts and a dense, immunostained extracellular matrix. Thus, although the dynamic presence of transforming growth factor-beta isoforms exemplifies its positive role in the wound repair process, its persistence together with its known potent effects on matrix accumulation, supports its role in scar formation.
为阐明转化生长因子β亚型（β1、β2和β3）在伤口修复中的作用，我们使用亚型特异性抗体，通过免疫组织化学定位，在绵羊皮肤切除和切开伤口后的21天内，检测潜伏型和成熟/活性转化生长因子β亚型的时空表达。虽然切除伤口和切开伤口显示出相似的转化生长因子β免疫反应模式，但我们发现在整个伤口修复过程中，潜伏型和成熟型转化生长因子β亚型存在不同的时空表达。具体而言，受伤后1天，伤口附近的上皮、表皮附属器以及肉芽组织的细胞和基质中，转化生长因子β亚型显著增加。此时，转化生长因子β3亚型最为丰富。最值得注意的是，受伤后1天，伤口附近的表皮对所有转化生长因子β亚型均呈现强烈的免疫反应。然而，源自毛囊和伤口边缘的迁移上皮，在重新上皮化完成之前，完全没有免疫反应性转化生长因子β。在炎性渗出物中，有一条明显的白细胞带，受伤后1天对转化生长因子β2和β3呈免疫反应，1天后对转化生长因子β1呈免疫反应。虽然转化生长因子β1和β2、潜伏型转化生长因子β2、转化生长因子β3和潜伏型转化生长因子β3免疫染色存在于众多成纤维细胞和其他真皮细胞中，但潜伏型转化生长因子β1仅与细胞外基质相关。一般来说，免疫反应性在受伤后第7天前一直很高，并随时间缓慢消退。然而，到第21天，免疫染色尚未恢复正常，原始伤口充满免疫反应性成纤维细胞和密集的、免疫染色的细胞外基质。因此，虽然转化生长因子β亚型的动态存在例证了其在伤口修复过程中的积极作用，但其持续存在以及其对基质积累的已知强效作用，支持了其在瘢痕形成中的作用。
