Thyroid horomone and wound healing: HIF-1 alpha A potential thyroid responsive protein. MMP-2, MMP-9, and TIMP-2 thyroid independent proteins.
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Wound healing is a dynamic and tightly regulated orchestration of cells and proteins. The process is generally subdivided into three stages that overlap in space and time; they are hemostasis, inflammation, and proliferation. Thyroid Hormone is observed to improve wound healing, but the mechanism underlying this phenomenon is not fully understood. Matrix Metalloproteinases (MMP) 2 and 9 are proteases that are capable of digesting a wide variety of extracellular matrix proteins, as well as growth factors. Each of these proteases has roles within normal wound healing, but are observed to be elevated in chronic diabetic ulcers. Tissue inhibitors of metalloproteinases-2 (TIMP-2) is a molecule capable of inhibiting all MMP's, but MMP-2 to a larger degree. TIMP-2 is observed to decrease in chronic diabetic ulcers. Hypoxia induced factor-1α(HIF-1α) has been observed to be a thyroid responsive gene in fibroblasts, but has roles in angiogenesis and keratinocyte migration as well. Exogenous HIF-1α has been shown to reestablish normal granulation tissue in diabetic skin. Human fibroblasts and keratinocytes were dosed with either 0M, 10^-8M, 10^-6M thyroid hormone in-vitro, and their cell lysates were analyzed via Western blots to detect the expression of MMP-2, MMP-9, TIMP-2 and HIF-1α. Protein expression relative to beta actin was determined for MMP-2, MMP-9 and TIMP-2 and analyzed by a one way ANOVA. The on or off nature of HIF-1α expression and small sample size prevented statistical analysis. None of the proteins examined displayed significantly altered expressions in response to thyroid hormone. However, HIF-1α, despite a small sample size, trended towards significance in both keratinocytes and fibroblast. Our results do not support that thyroid hormone mediates its improved wound healing via a pathway involving MMP-2, MMP-9 or TIMP-2. HIF-1α, however displays a great deal of promise as a thyroid responsive protein associated with improved wound healing.
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