title: Primary Cilia Negatively Regulate Melanogenesis in Melanocytes and Pigmentation in a Human Skin Model.
abstract: The primary cilium is an organelle protruding from the cell body that senses external stimuli including chemical, mechanical, light, osmotic, fluid flow, and gravitational signals. Skin is always exposed to the external environment and responds to external stimuli. Therefore, it is possible that primary cilia have an important role in skin. Ciliogenesis was reported to be involved in developmental processes in skin, such as keratinocyte differentiation and hair formation. However, the relation between skin pigmentation and primary cilia is largely unknown. Here, we observed that increased melanogenesis in melanocytes treated with a melanogenic inducer was inhibited by a ciliogenesis inducer, cytochalasin D, and serum-free culture. However, these inhibitory effects disappeared in GLI2 knockdown cells. In addition, activation of sonic hedgehog (SHH)-smoothened (Smo) signaling pathway by a Smo agonist, SAG inhibited melanin synthesis in melanocytes and pigmentation in a human skin model. On the contrary, an inhibitor of primary cilium formation, ciliobrevin A1, activated melanogenesis in melanocytes. These results suggest that skin pigmentation may be regulated partly by the induction of ciliogenesis through Smo-GLI2 signaling.
authors.affiliation: Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Gyeonggi-do, Republic of Korea.|R&D Unit, AmorePacific Corporation, Yongin, Gyeonggi-do, Republic of Korea.
authors.forename: Hyunjung
authors.initials: H
authors.lastname: Choi
authors.affiliation: Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Gyeonggi-do, Republic of Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Shin
authors.affiliation: Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Gyeonggi-do, Republic of Korea.
authors.forename: Eun Sung
authors.initials: ES
authors.lastname: Kim
authors.affiliation: Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Gyeonggi-do, Republic of Korea.
authors.forename: So Jung
authors.initials: SJ
authors.lastname: Park
authors.affiliation: R&D Unit, AmorePacific Corporation, Yongin, Gyeonggi-do, Republic of Korea.
authors.forename: Il-Hong
authors.initials: IH
authors.lastname: Bae
authors.affiliation: Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Gyeonggi-do, Republic of Korea.
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jo
authors.affiliation: Department of Medical Science, Korea University Ansan Hospital, Ansan, Gyeonggi-do, Republic of Korea.
authors.forename: In Young
authors.initials: IY
authors.lastname: Jeong
authors.affiliation: R&D Unit, AmorePacific Corporation, Yongin, Gyeonggi-do, Republic of Korea.
authors.forename: Hyoung-June
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: R&D Unit, AmorePacific Corporation, Yongin, Gyeonggi-do, Republic of Korea.
authors.forename: Youngjin
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Medical Science, Korea University Ansan Hospital, Ansan, Gyeonggi-do, Republic of Korea.
authors.forename: Hea Chul
authors.initials: HC
authors.lastname: Park
authors.affiliation: Biomedical Research Institute, MEDIPOST Corporation, Seongnam, Gyeonggi-do, Republic of Korea.
authors.forename: Hong Bae
authors.initials: HB
authors.lastname: Jeon
authors.affiliation: Department of Pharmacology, Wonju College of Medicine, Yonsei University, Wonju, Gangwon-do, Republic of Korea.
authors.forename: Ki Woo
authors.initials: KW
authors.lastname: Kim
authors.affiliation: R&D Unit, AmorePacific Corporation, Yongin, Gyeonggi-do, Republic of Korea.
authors.forename: Tae Ryong
authors.initials: TR
authors.lastname: Lee
authors.affiliation: Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, Gyeonggi-do, Republic of Korea.
authors.forename: Dong-Hyung
authors.initials: DH
authors.lastname: Cho
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002923:Cilia / Q000187:drug effects / Q000502:physiology*; D015638:Cytochalasin D / Q000494:pharmacology; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008543:Melanins / Q000096:biosynthesis*; D008544:Melanocytes / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000378:metabolism; D052999:Quinazolinones / Q000494:pharmacology; D015398:Signal Transduction; D012867:Skin / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D012879:Skin Physiological Phenomena / Q000187:drug effects; D012880:Skin Pigmentation / Q000187:drug effects / Q000502:physiology*; D000075746:Zinc Finger Protein Gli2
chemical_list: C082593:GLI2 protein, human; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D008543:Melanins; D009687:Nuclear Proteins; D052999:Quinazolinones; C509239:SHH protein, human; D000075746:Zinc Finger Protein Gli2; C000598071:ciliobrevin A; D015638:Cytochalasin D