title: Vasoactive intestinal peptide stimulates melanogenesis in B16F10 mouse melanoma cells via CREB/MITF/tyrosinase signaling.
abstract: Vasoactive intestinal peptide (VIP), one of the major skin neuropeptides, has been suggested to have active roles in the pathogenesis of inflammatory skin disorders such as atopic dermatitis and psoriasis, which can commonly cause post-inflammatory hyperpigmentation. However, the effect of VIP on melanogenesis remains unknown. In this study, we showed that the melanin contents, tyrosinase activity, and gene expression of tyrosinase and microphthalmia-associated transcription factor (MITF) were significantly increased by treatment with VIP in B16F10 mouse melanoma cells and the stimulatory melanogenic effect was further examined in human epidermal melanocytes (HEMns). In addition, phosphorylated levels of CRE-binding protein (CREB) and protein kinase A (PKA) were markedly increased after VIP treatment, but not p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase (ERK), or Akt, indicating the possible PKA-CREB signaling pathway involved in VIP-induced melanogenesis. This result was further verified by the fact that VIP induced increased melanin synthesis, and protein levels of phosphorylated CREB, MITF, tyrosinase were significantly attenuated by H89 (a specific PKA inhibitor). These data suggest that VIP-induced upregulation of tyrosinase through the CREB-MITF signaling pathway plays an important role in finding new treatment strategy for skin inflammatory diseases related pigmentation disorders.
authors.affiliation: Department of Dermatology, Seoul National University College of Medicine, Seoul, 110-744, Republic of Korea; Department of Dermatology, Yanbian University Hospital, Yanji, 133000, Jilin, China; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, 110-744, Republic of Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, 110-744, Republic of Korea. Electronic address: sunghwa531@gmail.com.
authors.forename: Xing-Hua
authors.initials: XH
authors.lastname: Yuan
authors.affiliation: Department of Dermatology, Seoul National University College of Medicine, Seoul, 110-744, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, 110-744, Republic of Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, 110-744, Republic of Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, 110-744, Republic of Korea.
authors.forename: Cheng
authors.initials: C
authors.lastname: Yao
authors.affiliation: Department of Dermatology, Seoul National University College of Medicine, Seoul, 110-744, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, 110-744, Republic of Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, 110-744, Republic of Korea.
authors.forename: Jang-Hee
authors.initials: JH
authors.lastname: Oh
authors.affiliation: Department of Dermatology, Seoul National University College of Medicine, Seoul, 110-744, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, 110-744, Republic of Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, 110-744, Republic of Korea.
authors.forename: Chi-Hyun
authors.initials: CH
authors.lastname: Park
authors.affiliation: Department of Dermatology, Seoul National University College of Medicine, Seoul, 110-744, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, 110-744, Republic of Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, 110-744, Republic of Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, 110-744, Republic of Korea.
authors.forename: Yu-Dan
authors.initials: YD
authors.lastname: Tian
authors.affiliation: Department of Dermatology, Seoul National University College of Medicine, Seoul, 110-744, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, 110-744, Republic of Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, 110-744, Republic of Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, 110-744, Republic of Korea.
authors.forename: Mira
authors.initials: M
authors.lastname: Han
authors.affiliation: Department of Dermatology, Seoul National University College of Medicine, Seoul, 110-744, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, 110-744, Republic of Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, 110-744, Republic of Korea.
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Department of Dermatology, Seoul National University College of Medicine, Seoul, 110-744, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, 110-744, Republic of Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, 110-744, Republic of Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, 110-744, Republic of Korea.
authors.forename: Jin Ho
authors.initials: JH
authors.lastname: Chung
authors.affiliation: Department of Dermatology, Yanbian University Hospital, Yanji, 133000, Jilin, China. Electronic address: zhjin621@gmail.com.
authors.forename: Zhe-Hu
authors.initials: ZH
authors.lastname: Jin
authors.affiliation: Department of Dermatology, Seoul National University College of Medicine, Seoul, 110-744, Republic of Korea; Laboratory of Cutaneous Aging Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, 110-744, Republic of Korea; Institute of Human-Environment Interface Biology, Medical Research Center, Seoul National University, Seoul, 110-744, Republic of Korea; Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, 110-744, Republic of Korea. Electronic address: ivymed27@gmail.com.
authors.forename: Dong Hun
authors.initials: DH
authors.lastname: Lee
mesh_terms: D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D008543:Melanins / Q000096:biosynthesis*; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D008543:Melanins; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D012333:RNA, Messenger; D014660:Vasoactive Intestinal Peptide; D014442:Monophenol Monooxygenase
keywords: B16F10 mouse melanoma cell; CREB; MITF; Melanogenesis; Tyrosinase; Vasoactive intestinal peptide