title: A systems-biological study on the identification of safe and effective molecular targets for the reduction of ultraviolet B-induced skin pigmentation.
abstract: Melanogenesis is the process of melanin synthesis through keratinocytes-melanocytes interaction, which is triggered by the damaging effect of ultraviolet-B (UVB) rays. It is known that melanogenesis influences diverse cellular responses, including cell survival and apoptosis, via complex mechanisms of feedback and crosstalk. Therefore, an attempt to suppress melanin production by modulating the melanogenesis pathway may induce perturbations in the apoptotic balance of the cells in response to UVB irradiation, which results in various skin diseases such as melasma, vitiligo, and skin cancer. To identify such appropriate target strategies for the reduction of UVB-induced melanin synthesis, we reconstructed the melanogenesis signaling network and developed a Boolean network model. Mathematical simulations of the melanogenesis network model revealed that the inhibition of beta-catenin in the melanocytes effectively reduce melanin production while having minimal influence on the apoptotic balance of the cells. Exposing cells to a beta-catenin inhibitor decreased pigmentation but did not significantly change the B-cell Chronic lymphocytic leukemia/lymphoma 2 expression, a potent regulator of apoptotic balance. Thus, our systems analysis suggests that the inhibition of beta-catenin may be the most appropriate target strategy for the reduction of UVB-induced skin pigmentation.
authors.affiliation: 1] Laboratory for Systems Biology and Bio-Inspired Engineering, Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Republic of Korea [2] Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Republic of Korea.
authors.forename: Ho-Sung
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Skin Research Institute, Amorepacific R&D center, Gyeonggi-do, 446-729, Republic of Korea.
authors.forename: Myeong-Jin
authors.initials: MJ
authors.lastname: Goh
authors.affiliation: Laboratory for Systems Biology and Bio-Inspired Engineering, Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Republic of Korea.
authors.forename: Junil
authors.initials: J
authors.lastname: Kim
authors.affiliation: Laboratory for Systems Biology and Bio-Inspired Engineering, Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Republic of Korea.
authors.forename: Tae-Jun
authors.initials: TJ
authors.lastname: Choi
authors.affiliation: Skin Research Institute, Amorepacific R&D center, Gyeonggi-do, 446-729, Republic of Korea.
authors.forename: Hae
authors.initials: H
authors.lastname: Kwang Lee
authors.affiliation: Skin Research Institute, Amorepacific R&D center, Gyeonggi-do, 446-729, Republic of Korea.
authors.forename: Yong
authors.initials: Y
authors.lastname: Joo Na
authors.affiliation: 1] Laboratory for Systems Biology and Bio-Inspired Engineering, Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Republic of Korea [2] Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, 305-701, Republic of Korea.
authors.forename: Kwang-Hyun
authors.initials: KH
authors.lastname: Cho
mesh_terms: D002478:Cells, Cultured; D004822:Epididymis / Q000166:cytology; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000378:metabolism / Q000528:radiation effects; D008954:Models, Biological; D008962:Models, Theoretical; D015203:Reproducibility of Results; D015398:Signal Transduction; D012880:Skin Pigmentation / Q000502:physiology* / Q000528:radiation effects*; D049490:Systems Biology / Q000379:methods; D014466:Ultraviolet Rays
chemical_list: D008543:Melanins