Author for correspondence: Wen-Jun Lan, Laboratory for Drug Discovery, Shandong Institute of Light Industry, Jinan 250353, China (fax +86-531-89631191, e-mail [email protected]).

Read the full text

About

PDF

Tools

Share a link

Email
Wechat
Bluesky

Abstract

Abstract: Geniposide is an iridoid glycoside isolated from the fruit of Gardenia jasminoides Ellis used as a Chinese traditional medicine for treatment of generalized vitiligo. Stem cell factor from keratinocyte recognizes and activates its receptor c-kit carried by melanocyte to potent enhance melanocytic melanogenesis that can be suppressed by norepinephrine. This study addresses the action and mechanism of geniposide enhancing melanogenesis in norepinephrine-exposed normal human epidermal melanocyte. Flow cytometry results from this study exhibited the augmentation effect of geniposide on production of c-kit receptor by norepinephrine-exposed normal human epidermal melanocyte. However, geniposide did not affect the production of stem cell factor by norepinephrine-exposed normal human epidermal keratinocyte assessed by cellular enzyme-linked immunosorbent assay (ELISA). ELISA indicated that at the presence of stem cell factor, geniposide was capable of elevating the level of extracellular signal-regulated kinase 1/2 phosphorylation within norepinephrine-exposed normal human epidermal melanocyte, which is known to be involved in stem cell factor/c-kit downstream signalling. And inhibition of c-kit with inhibitory antibody K44.2 completely blocked the increase in geniposide-stimulated extracellular signal-regulated kinase 1/2 phosphorylation. In addition, spectrophotometry demonstrated the enhancement effect of geniposide on melanogenesis (tyrosinase activity and melanin production) in norepinephrine-exposed normal human epidermal melanocyte at the presence of stem cell factor, which was blocked by c-kit inhibitory antibody K44.2. Data from this study suggest that geniposide can enhance melanogenesis by stem cell factor/c-kit signalling in which the expression of c-kit receptor is augmented in norepinephrine-exposed normal human epidermal melanocyte.

References

1 Namazi MR. Prescribing cyclic antidepressants for vitiligo patients: which agents are superior, which are not? Psychother Psychosom 2003; 72: 361–2.
10.1159/000073036
PubMed Web of Science® Google Scholar
2 Hann SK, Chun WH. Autocytotoxic hypothesis for the destruction of melanocytes as the cause of vitiligo. In: SK Hann, JJ Nordlund (eds). vitiligo. 1. Blackwell Scientific Publications, Oxford, UK, 2000; 137–41.
10.1002/9780470760116.ch17
Google Scholar
3 Passeron T, Ortonne JP. Physiopathology and genetics of vitiligo. J Autoimmun 2005; 25: 63–8.
10.1016/j.jaut.2005.10.001
CAS PubMed Web of Science® Google Scholar
4 Wankowicz-Kalinska A, Van Den Wijngaard RM, Tiggers BJ, Westerhof W, Ogg GS, Cerundolo V et al . Immunopolarization of CD4+ and CD8+ T cells to type-1-like is associated with melanocyte loss in human vitiligo. Lab Invest 2003; 83: 683–95.
10.1097/01.LAB.0000069521.42488.1B
CAS PubMed Web of Science® Google Scholar
5 Schallreuter KU, Moore J, Wood JM, Beazley WD, Gaze DC, Tobin DJ et al . In vivo and in vitro evidence for hydrogen peroxide (H₂O₂) accumulation in the epidermis of patients with vitiligo and its successful removal by a UVB-activated pseudocatalase. J Investig Dermatol Symp Proc 1999; 4: 91–6.
10.1038/sj.jidsp.5640189
CAS PubMed Web of Science® Google Scholar
6 Hemesath TJ, Price ER, Takemoto C, Badalian T, Fisher DE. MAP kinase links the transcription factor microphthalmia to c-kit signalling in melanocytes. Nature 1998; 391: 298–301.
10.1038/34681
CAS PubMed Web of Science® Google Scholar
7 Na YJ, Baek HS, Ahn SM, Shin HJ, Chang IS, Hwang JS. [4-t-Butylphenyl]-N-(4-imidazol-1-yl phenyl)sulfonamide (ISCK03) inhibits SCF/c-kit signaling in 501 mel human melanoma cells and abrogates melanin production in mice and brownish guinea pigs. Biochem Pharmacol 2007; 74: 780–6.
10.1016/j.bcp.2007.05.028
CAS PubMed Web of Science® Google Scholar
8 Norris A, Todd C, Graham A, Quinn AG, Thody AJ. The expression of the c-kit receptor by epidermal melanocytes may be reduced in vitiligo. Br J Dermatol 1996; 134: 299–306.
10.1111/j.1365-2133.1996.tb07618.x
CAS PubMed Web of Science® Google Scholar
9 Imokawa G. Autocrine and paracrine regulation of melanocytes in human skin and in pigmentary disorders. Pigment Cell Res 2004; 17: 96–110.
10.1111/j.1600-0749.2003.00126.x
CAS PubMed Web of Science® Google Scholar
10 Lee YA, Kim NH, Choi WI, Youm YH. Less keratinocyte-derived factors related to more keratinocyte apoptosis in depigmented than normally pigmented suction-blistered epidermis may cause passive melanocyte death in vitiligo. J Invest Dermatol 2005; 124: 976–83.
10.1111/j.0022-202X.2005.23667.x
CAS PubMed Web of Science® Google Scholar
11 Kitamura R, Tsukamoto K, Harada K, Shimizu A, Shimada S, Kobayashi T et al . Mechanisms underlying the dysfunction of melanocytes in vitiligo epidermis: role of SCF/KIT protein interactions and its downstream effector, MITF-M. J Pathol 2004; 202: 463–75.
10.1002/path.1538
CAS PubMed Web of Science® Google Scholar
12 Suzuki Y, Kondo K, Ikeda Y, Umemura K. Antithrombotic effect of geniposide and genipin in the mouse thrombosis model. Planta Med 2001; 67: 807–10.
10.1055/s-2001-18842
CAS PubMed Web of Science® Google Scholar
13 Koo HJ, Lee S, Shin KH, Kim BC, Lim CJ, Park EH. Geniposide, an anti-angiogenic compound from the fruits of Gardenia jasminoides. Planta Med 2004; 70: 467–9.
10.1055/s-2004-818978
CAS PubMed Web of Science® Google Scholar
14 Kuo WH, Chou FP, Young SC, Chang YC, Wang CJ. Geniposide activates GSH S-transferase by the induction of GST M1 and GST M2 subunits involving the transcription and phosphorylation of MEK-1 signaling in rat hepatocytes. Toxicol Appl Pharmacol 2005; 208: 155–62.
10.1016/j.taap.2005.02.013
CAS PubMed Web of Science® Google Scholar
15 Berens W, Van Den Bossche K, Yoon TJ, Westbroek W, Valencia JC, Out CJ et al . Different approaches for assaying melanosome transfer. Pigment Cell Res 2005; 18: 370–81.
10.1111/j.1600-0749.2005.00263.x
CAS PubMed Web of Science® Google Scholar
16 Sakai A. Inhibition of endothelial cell adhesion molecule expression with SJC13, an azaindolidine derivative, in vitro. Inflamm Res 1996; 45: 224–9.
10.1007/BF02259607
CAS PubMed Web of Science® Google Scholar
17 Lawrie A, Spiekerkoetter E, Martinez EC, Ambartsumian N, Sheward WJ, MacLean MR et al . Interdependent serotonin transporter and receptor pathways regulate S100A4/Mts1, a gene associated with pulmonary vascular disease. Circ Res 2005; 97: 227–35.
10.1161/01.RES.0000176025.57706.1e
CAS PubMed Web of Science® Google Scholar
18 Maeda K, Fukuda M. Arbutin: mechanism of its depigmenting action in human melanocyte culture. J Pharmacol Exp Ther 1996; 276: 765–9.
CAS PubMed Web of Science® Google Scholar
19 Friedmann PS, Gilchrest BA. Ultraviolet radiation directly induces pigment production by cultured human melanocytes. J Cell Physiol 1987; 133: 88–94.
10.1002/jcp.1041330111
CAS PubMed Web of Science® Google Scholar
20 Longley BJ Jr, Morganroth GS, Tyrrell L, Ding TG, Anderson DM, Williams DE et al . Altered metabolism of mast-cell growth factor (c-kit ligand) in cutaneous mastocytosis. N Engl J Med 1993; 328: 1302–7.
10.1056/NEJM199305063281803
PubMed Web of Science® Google Scholar
21 Hamann K, Haas N, Grabbe J, Czarnetzki BM. Expression of stem cell factor in cutaneous mastocytosis. Br J Dermatol 1995; 133: 203–8.
10.1111/j.1365-2133.1995.tb02616.x
CAS PubMed Web of Science® Google Scholar
22 Cooksey CJ, Garratt PJ, Land EJ, Paveli S, Ramsden CA, Riley PA et al . Evidence of the indirect formation of the catecholic intermediate substrate responsible for the autoactivation kinetics of tyrosinase. J Biol Chem 1997; 272: 26226–35.
10.1074/jbc.272.42.26226
CAS PubMed Web of Science® Google Scholar
23 Hachiya A, Kobayashi A, Yoshida Y, Kitahara T, Takema Y, Imokawa G. Biphasic expression of two paracrine melanogenic cytokines, stem cell factor and endothelin-1, in ultraviolet B-induced human melanogenesis. Am J Pathol 2004; 165: 2099–109.
10.1016/S0002-9440(10)63260-9
CAS PubMed Web of Science® Google Scholar
24 Hachiya A, Kobayashi A, Ohuchi A, Takema Y, Imokawa G. The paracrine role of stem cell factor/c-kit signaling in the activation of human melanocytes in ultraviolet-B-induced pigmentation. J Invest Dermatol 2001; 116: 578–86.
10.1046/j.1523-1747.2001.01290.x
CAS PubMed Web of Science® Google Scholar
25 Prignano F, Gerlini G, Salvatori B, Orlando C, Mazzoli S, Pimpinelli N et al . Stem cell factor affects tumour progression markers in metastatic melanoma cells. Clin Exp Metastasis 2006; 23: 177–86.
10.1007/s10585-006-9027-9
CAS PubMed Web of Science® Google Scholar
26 Huang S, Luca M, Gutman M, McConkey DJ, Langley KE, Lyman SD et al . Enforced c-KIT expression renders highly metastatic human melanoma cells susceptible to stem cell factor-induced apoptosis and inhibits their tumorigenic and metastatic potential. Oncogene 1996; 13: 2339–47.
CAS PubMed Web of Science® Google Scholar
27 Schallreuter KU. Epidermal adrenergic signal transduction as part of the neuronal network in the human epidermis. J Investig Dermatol Symp Proc 1997; 2: 37–40.
10.1038/jidsymp.1997.9
CAS PubMed Web of Science® Google Scholar
28 Yee NS, Langen H, Besmer P. Mechanism of kit ligand, phorbol ester, and calcium-induced down-regulation of c-kit receptors in mast cells. J Biol Chem 1993; 268: 14189–201.
10.1016/S0021-9258(19)85226-2
CAS PubMed Web of Science® Google Scholar
29 Liaw J, Chao YC. Effect of in vitro and in vivo aerosolized treatment with geniposide on tracheal permeability in ovalbumin-induced guinea pigs. Eur J Pharmacol 2001; 433: 115–21.
10.1016/S0014-2999(01)01506-0
CAS PubMed Web of Science® Google Scholar
30 Hou L, Panthier JJ, Arnheiter H. Signaling and transcriptional regulation in the neural crest-derived melanocyte lineage: interactions between KIT and MITF. Development 2000; 127: 5379–89.
10.1242/dev.127.24.5379
CAS PubMed Web of Science® Google Scholar
31 Kim DS, Park SH, Kwon SB, Park ES, Huh CH, Youn SW et al . Sphingosylphosphorylcholine-induced ERK activation inhibits melanin synthesis in human melanocytes. Pigment Cell Res 2006; 19: 146–53.
10.1111/j.1600-0749.2005.00287.x
CAS PubMed Web of Science® Google Scholar
32 Yanase H, Ando H, Horikawa M, Watanabe M, Mori T, Matsuda N. Possible involvement of ERK 1/2 in UVA-induced melanogenesis in cultured normal human epidermal melanocytes. Pigment Cell Res 2001; 14: 103–9.
10.1034/j.1600-0749.2001.140205.x
CAS PubMed Web of Science® Google Scholar
33 Takeyama R, Takekoshi S, Nagata H, Osamura RY, Kawana S. Quercetin-induced melanogenesis in a reconstituted three-dimensional human epidermal model. J Mol Histol 2004; 35: 157–65.
10.1023/B:HIJO.0000023388.51625.6c
CAS PubMed Web of Science® Google Scholar

Citing Literature

Volume103, Issue1

July 2008

Pages 88-93

Geniposide Enhances Melanogenesis by Stem Cell Factor/c-Kit Signalling in Norepinephrine-Exposed Normal Human Epidermal Melanocyte

Abstract

References

Citing Literature

References

Information

About Wiley Online Library

Help & Support

Opportunities

Connect with Wiley

Geniposide Enhances Melanogenesis by Stem Cell Factor/c-Kit Signalling in Norepinephrine-Exposed Normal Human Epidermal Melanocyte

Abstract

References

Citing Literature

References

Related

Information