Effects of endothelin-1 on fibroblasts from type 2 diabetic patients: Possible role in wound healing and tissue repair

Endothelin-1 (ET-1) promotes the contractile ability of fibroblasts, essential for wound closure and reconstitution of the dermis. Wound healing is impaired in type 2 diabetic patients (D). We compared the effect of ET-1 on proliferative transforming growth factor (TGFβ₁) expression, fibronectin and laminin release), differentiative [α-smooth muscle actin (α-SMA) expression] and inflammatory [monocyte chemo-attractant protein (MCP-1) and interleukin-6 (IL-6) expression] responses in skin fibroblasts of healthy subjects (C) and D, testing the relative role of ET_A and ET_B receptors in mediating these responses. ET-1 did not influence TGFβ₁, fibronectin or laminin production. α-SMA was more abundant and more stimulated in D, as well as MCP-1 and IL-6 expression and release. These effects were prevented by BMS-182874, selective antagonist of ET_A, more abundant than ET_B in both cell strains and whose expression rose more in D than C upon stimulation with ET-1. This peculiar pattern of responses to ET-1, presumably acquired during the chronic in vivo exposure to hyperglycemia along the natural history of the disease, may partially explain the increased susceptibility of D to chronic ulcerations.