Abstract
BACKGROUND: Keloids are growing scars that arise from injury to the reticular dermis and subsequent chronic local inflammation. The latter may be promoted by vascular hyperpermeability, which permits the ingress of chronic inflammatory cells/factors. Cutaneous capillaries consist of endothelial cells that generate, and are anchored by, a vascular basement membrane (VBM). Because VBM blocks immune cells/factors ingress, we investigated whether keloids are associated with altered VBM structure and/or VBM component expression by local endothelial cells. METHODS: In total, 54 keloid (n = 27) and adjacent normal skin (n = 27) samples from 14 patients underwent transmission electron microscopy (TEM). Cross-sections of whole capillaries were identified. VBM thickness, continuity, and the number of layers in keloid and normal skin tissues were quantified. The differential expression of 222 previously reported VBM component genes in keloid and normal skin endothelial cells was analyzed using the GSE121618-microarray dataset. RESULTS: TEM images showed that keloid VBMs were significantly thinner than adjacent skin VBMs (0.053 versus 0.078 nm; P < 0.001). They were also greatly fragmented (continuity was 46% versus 85% in normal skin; P < 0.001) and had fewer (1.2 versus 2.4) layers (P < 0.001). Keloidal endothelial cells demonstrated downregulation of 22 genes, including papilin, laminin-α5, and laminin-α2, and upregulation of 28 genes, including laminin-β1, laminin-β2, laminin-γ1, and laminin-γ2. CONCLUSIONS: VBMs are greatly fragmented in keloids. These changes support the notion that keloids are initiated/promoted, at least partly, by vascular hyperpermeability.