TY - JOUR T1 - Importance of UDP-glucuronosyltransferase 1A1 Expression in Skin and its Induction by Ultraviolet B in Neonatal Hyperbilirubinemia JF - Molecular Pharmacology JO - Mol Pharmacol DO - 10.1124/mol.113.088112 SP - mol.113.088112 AU - Kyohei Sumida AU - Makiko Kawana AU - Emi Kouno AU - Tomoo Itoh AU - Shuhei Takano AU - Tomoya Narawa AU - Robert H Tukey AU - Ryoichi Fujiwara Y1 - 2013/08/15 UR - http://molpharm.aspetjournals.org/content/early/2013/08/15/mol.113.088112.abstract N2 - UDP-glucuronosyltransferase (UGT) 1A1 is the sole enzyme that can metabolize bilirubin. Human infants physiologically develop hyperbilirubinemia due to inadequate expression of UGT1A1 in the liver. While phototherapy using blue light is effective in preventing jaundice, sunlight has also been suggested, but without conclusive evidence, to reduce serum bilirubin levels. We investigated the mRNA expression pattern of human UGT1A1 in human skin, human skin keratinocyte (HaCaT) cells, and skin of humanized UGT1 mice. The effects of ultraviolet B (UVB)-irradiation on the expression of UGT1A1 in the HaCaT cells were also examined. Multiple UGT1A isoforms including UGT1A1 were expressed in human skin and HaCaT cells. When HaCaT cells were treated with UVB-exposed tryptophan, UGT1A1 mRNA and activity were significantly induced. The treatment of the HaCaT cells with 6-formylindolo[3,2-b]carbazole (FICZ), which is one of the tryptophan derivatives formed by UVB, resulted in an induction of UGT1A1 mRNA and activity. In neonates the expression of UGT1A1 was greater in the skin, while in adults UGT1A1 was mainly expressed in the liver. Treatment of humanized UGT1 mice with UVB resulted in a reduction of serum bilirubin levels, along with increased UGT1A1 expression and activity in the skin. Our data revealed a protective role of UGT1A1 expressed in the skin against neonatal hyperbilirubinemia. Sunlight, a natural and free source of light, makes it possible to treat neonatal jaundice, while allowing mothers to breast-feed neonates. ER -