A role for thyroid hormone in wound healing through keratin gene expression

The importance of thyroid hormone (TH) in wound healing is not well understood. To gain insight, we evaluated the impact of TH deficiency on wound-healing genes in cultured keratinocytes. By RT-PCR, keratin 6a (K6a) and 16 (K16) gene expression in TH replete cells was 3.8- (P < 0.005) and 1.9-fold (P < 0.05) greater, respectively, than expression in TH-deficient cells. By real-time PCR, TH replete cell expression of K6a, K16, and K17 was greater than in deficient cells: 18- (P < 0.001), 10- (P < 0.001), and 4-fold (P < 0.005), respectively. To examine TH requirement for optimal wound healing, we contrasted TH-deficient vs. ip T₃-treated mice. Four days after wounding, ip T₃-treated mice had twice the degree of wound closure as hypothyroid mice (P < 0.001). By RT-PCR, K6a and K17 gene expression from control mouse skin was greater than from hypothyroid mouse skin: 5- (P < 0.001) and 1.7-fold (P < 0.05), respectively. T₃ is necessary for the keratinocyte proliferation required for optimal wound healing. T₃ exerts influence by stimulating expression of the wound-healing keratin genes. Thus, for hypothyroid patients undergoing surgery that cannot be delayed until euthyroidism is achieved, our data support T₃ treatment for the perioperative period.