Thyroid hormone analogue stimulates keratinocyte proliferation but inhibits cell differentiation in epidermis

Gross clinical manifestations of thyroid hormone (TH) imbalance are often first seen in the skin where TH plays an integral role in sustaining natural function. Although mounting evidence suggests that TH plays an important role in epidermal proliferation and wound healing, the physiologic role of thyroid hormone in skin is not well understood. In the current study, we investigated the effect of a natural thyroid hormone analogue - 3, 3′, 5-triiodo-thyroacetic acid (TRIAC) on regulating proliferation and differentiation and its possible molecular mechanism in normal human epidermal keratinocytes and C57BL/6 mice. We determined that TRIAC could stimulate epidermal thickening in mice and promote human keratinocyte proliferation by activating Cyclin D1 expression and promoting entrance into S phase. Moreover, TRIAC might inhibit cell differentiation through repressing the expression of Casein Kinase 1 (CK1), which is a key regulatory protein involved in the control of cell differentiation. Taken together, our data explored the physiologic effect of TRIAC on skin and the possible molecular mechanism of TRIAC, which might be an interesting compound for the treatment of hyperkeratotic skin disorders.