title: Endothelin-1 enhances the melanogenesis via MITF-GPNMB pathway.
abstract: Endothelin-1 (ET-1) plays an indispensable role in epidermal pigmentation in hyperpigmentary disorders due to a central role in melanogenesis. Nevertheless, precise mechanism involved in ET-1-induced hyperpigmentation is still undefined. Glycoprotein (transmembrane) non-metastatic melanoma protein b (GPNMB) is a key element in melanosome formation. Therefore, we speculated that GPNMB was correlated with ET-1-induced pigmentation. After culturing with ET-1, melanin synthesis was significantly up-regulated, accompanying with increased expression of GPNMB and microphthalmia- associated transcription factor (MITF). Total number of melanosomes and melanin synthesis were sharply reduced via GPNMB-siRNA transfection, indicating ET-1-induced pigmentation by GPNMB-dependent manner. Furthermore, MITFsiRNA transfection strikingly inhibited GPNMB expression and the melanogenesis, and this suppression failed to be alleviated by ET-1 stimulation. All of these results demonstrated that ET-1 can trigger melanogenesis via the MITF-regulated GPNMB pathway. Taken together, these findings will provide a new explanation of how ET-1 induces hyperpigmentation, and possibly supply a new strategy for cosmetic studies.
authors.affiliation: Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Yuan
authors.forename: Dongguang
authors.initials: D
authors.lastname: Li
authors.forename: Weijie
authors.initials: W
authors.lastname: Gu
authors.forename: Tianwen
authors.initials: T
authors.lastname: Gao
mesh_terms: D002478:Cells, Cultured; D019332:Endothelin-1 / Q000494:pharmacology*; D006801:Humans; D008543:Melanins / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020460:Melanosomes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051739:Microphthalmia-Associated Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D010858:Pigmentation / Q000187:drug effects; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D019332:Endothelin-1; C503042:GPNMB protein, human; D008543:Melanins; D008562:Membrane Glycoproteins; D051739:Microphthalmia-Associated Transcription Factor; D034741:RNA, Small Interfering