All-trans retinoic acid attenuates ultraviolet radiation-induced down-regulation of aquaporin-3 and water permeability in human keratinocytes

作     者：Amaral,A Kouttab,N 

作者机构：Providence Coll Dept Biol Providence RI 02918 USA. Brown Univ Dept Mol Microbiol & Immunol Providence RI 02912 USA. Nanjing Med Univ Dept Dermatol Nanjing Peoples R China. Boston Univ Roger Williams Med Ctr Dept Pathol Providence RI USA. Providence Coll Dept Biol Providence RI 02918 USA. Brown Univ Dept Mol Microbiol & Immunol Providence RI 02912 USA. Nanjing Med Univ Dept Dermatol Nanjing Peoples R China. Boston Univ Roger Williams Med Ctr Dept Pathol Providence RI USA. 

出 版 物：《南京医科大学学报(自然科学版)》 (Journal of Nanjing Medical University(Natural Sciences))

年 卷 期：2008年第5期

页      面：639-639页

学科分类：1002[医学-临床医学] 100203[医学-老年医学] 10[医学] 

主　　题：skin in-vivo growth-factor receptor heparin-binding egf photoaged skin topical tretinoin epithelial-cells survival pathway irradiation activation inhibition 

摘      要：One of the major characteristics of human skin photoaging induced by ultraviolet(UV) radiation is the dehydration of theskin. Water movement across plasma membrane occurs via diffusion through lipid bilayer and via aquaporins (AQPs). We find thatUV induces aquaporin-3 (AQP3) down-regulation in human skin keratinocytes. MEK/ERK inhibitors PD98059 and U0126 inhibitUV-induced down-regulation of AQP3. Antioxidant N-acetyl-L-cysteine or NAC blocks UV-induced MEK/ERK activation and down-regulation of AQP3. All-trans retinoic acid or atRA, while alone inducing AQP3 expression, attenuates UV-induced down-regulationof AQP3 and water permeability. Using special inhibitors, we find that activation of EGFR and inhibition on ERK activation are in-volved in atRA’s protective effects against UV-induced AQP3 down-regulation. Using specific AQP3’s water transport inhibitors andsiRNA knockdown, we observe that AQP3 is involved in cell migration and in vitro wound healing. UV-induced AQP3 down-regula-tion results in reduced water permeability, decreased cell migration, and delayed wound healing, which are attenuated by atRApretreatment. We conclude that atRA protects against UV-induced down-regulation AQP3 and decrease in water permeability, reduc-tion in cell migration and delayed in vitro wound healing via trans-activation of EGFR and inhibition on ROS-mediated MEK/ERKpathway. This novel finding provides evidence to support possible involvement of AQP3 in UV induced skin dehydration.