Ghahary A, Shen Y J, Wang R, Scott P G, Tredget E E
Department of Surgery, University of Alberta, Edmonton, Canada.
Mol Cell Biochem. 1998 Jun;183(1-2):1-9. doi: 10.1023/a:1006890212478.
The migration of epithelial cells from dermal appendages toward the wound surface is essential for re-epithelialization of partial thickness burn injuries. This study provides evidence that these cells in vivo synthesize a mitogenic and fibrogenic factor, insulin-like growth factor-1 (IGF-1), which may promote the development of the post-burn fibroproliferative disorder, hypertrophic scarring (HSc). An evaluation of 7 post-burn hypertrophic scars, 7 normal skin samples obtained from the same patients and 4 mature scars revealed that IGF-1 expressing cells from the disrupted sweat glands tend to reform small sweat glands of 4-10 cells/gland in post-burn HSc. The number of these cells increases with time and the glands become larger in mature scar. Other epithelial cells such as those found in sebaceous glands and basal and suprabasal keratinocytes, also express IGF-1 protein and mRNA as detected by Northern and RT-PCR analysis of RNA obtained from whole skin and separated epidermis and dermis. However, cultured keratinocytes did not express mRNA for IGF-1. Histological comparisons between normal and HSc sections show no mature sebaceous glands in dermal fibrotic tissues but the number of IGF-1 producing cells including infiltrated immune cells was markedly higher in the dermis of hypertrophic scar tissues relative to that of the normal control. In these tissues, but not in normal dermis, IGF-1 protein was found associated with the extracellular matrix. By in situ hybridization, IGF-1 mRNA was localized to both epithelial and infiltrated immune cells. Collectively, these findings suggest that in normal skin, fibroblasts have little or no access to diffusible IGF-1 expressed by epithelial cells of the epidermis, sweat and sebaceous glands; while following dermal injury when these structures are disrupted, IGF-1 may contribute to the development of fibrosis through its fibrogenic and mitogenic functions. Reformation of sweat glands during the later stages of healing may, therefore, limit this accessibility, and lead to scar maturation.
上皮细胞从皮肤附属器向创面迁移对于浅度烧伤创面的再上皮化至关重要。本研究提供了证据，表明这些体内细胞合成一种促有丝分裂和促纤维化因子，即胰岛素样生长因子-1（IGF-1），其可能促进烧伤后纤维增生性疾病——肥厚性瘢痕（HSc）的发展。对7例烧伤后肥厚性瘢痕、从同一患者获取的7份正常皮肤样本以及4份成熟瘢痕的评估显示，在烧伤后HSc中，来自受损汗腺的IGF-1表达细胞倾向于重新形成由4 - 10个细胞/腺组成的小汗腺。这些细胞的数量随时间增加，且在成熟瘢痕中腺体会变得更大。通过对从全皮以及分离的表皮和真皮获取的RNA进行Northern印迹和逆转录聚合酶链反应（RT-PCR）分析检测发现，其他上皮细胞，如皮脂腺中的上皮细胞以及基底和基底上层角质形成细胞，也表达IGF-1蛋白和信使核糖核酸（mRNA）。然而，培养的角质形成细胞不表达IGF-1的mRNA。正常组织切片与HSc组织切片的组织学比较显示，真皮纤维化组织中无成熟皮脂腺，但相对于正常对照，肥厚性瘢痕组织真皮中包括浸润免疫细胞在内的产生IGF-1的细胞数量明显更高。在这些组织中而非正常真皮中，发现IGF-1蛋白与细胞外基质相关。通过原位杂交，IGF-1 mRNA定位于上皮细胞和浸润免疫细胞。总体而言，这些发现表明，在正常皮肤中，成纤维细胞很少或无法接触到由表皮、汗腺和皮脂腺的上皮细胞表达的可扩散IGF-1；而在皮肤损伤后，当这些结构被破坏时，IGF-1可能通过其促纤维化和促有丝分裂功能促进纤维化的发展。因此，在愈合后期汗腺的重新形成可能会限制这种可及性，并导致瘢痕成熟。
