Skip to main content
Top
Published in: Archives of Dermatological Research 4/2018

01-05-2018 | Original Paper

Effect of Dickkopf1 on the senescence of melanocytes: in vitro study

Authors: Seema Rani, Rakhee Chauhan, Davinder Parsad, Ravinder Kumar

Published in: Archives of Dermatological Research | Issue 4/2018

Login to get access

Abstract

Fibroblasts secrete several growth factors which are important for the regulation of skin pigmentation. Dickkopf1 (DKK1) is also secreted by fibroblasts which inhibit the growth and function of melanocytes. Therefore, the study was designed to check the role of DKK1 in vitiligo pathogenesis. This study confirmed the higher expression of DKK1 in lesional skin of vitiligo patients. In vitro effect of DKK1 on cultured melanocytes revealed decrease in the melanocytes proliferation and pigmentation. In vitro effect of DKK1 was then checked on the melanocytes senescence and found that DKK1 induced senescence in the treated melanocytes. Expression of senescence markers was significantly higher in DKK1 treated melanocytes. This study suggests that higher expression of DKK1 in the dermis induced senescence in melanocytes that may lead to hypopigmentation and play role in vitiligo pathogenesis.
Literature
1.
go back to reference Andl T, Reddy S, Gaddapara T, Millar SE (2002) Wnt signals are required for the initiation of hair follicle development. Dev Cell 2:643–653CrossRefPubMed Andl T, Reddy S, Gaddapara T, Millar SE (2002) Wnt signals are required for the initiation of hair follicle development. Dev Cell 2:643–653CrossRefPubMed
2.
3.
go back to reference Cardinali G, Kovacs D, Giglio MD, Cota C, Aspite N et al (2009) A kindred with familial progressive hyperpigmentation-like disorder: implication of fibroblast-derived growth factors in pigmentation. Eur J Dermatol 19:469–473PubMed Cardinali G, Kovacs D, Giglio MD, Cota C, Aspite N et al (2009) A kindred with familial progressive hyperpigmentation-like disorder: implication of fibroblast-derived growth factors in pigmentation. Eur J Dermatol 19:469–473PubMed
4.
go back to reference Duval C, Cohen C, Chagnoleau C, Flouret V, Bourreau E et al (2014) Key regulatory role of dermal fibroblasts in pigmentation as demonstrated using a reconstructed skin model: impact of photo-aging. PLoS One 9(12):e114182CrossRefPubMedPubMedCentral Duval C, Cohen C, Chagnoleau C, Flouret V, Bourreau E et al (2014) Key regulatory role of dermal fibroblasts in pigmentation as demonstrated using a reconstructed skin model: impact of photo-aging. PLoS One 9(12):e114182CrossRefPubMedPubMedCentral
5.
go back to reference Glinka A, Wu W, Delius H, Monaghan AP, Blumenstock C, Niehrs C (1998) Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction. Nat 391:357–362CrossRef Glinka A, Wu W, Delius H, Monaghan AP, Blumenstock C, Niehrs C (1998) Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction. Nat 391:357–362CrossRef
7.
go back to reference Koch S, Nava P, Addis C, Kim W, Denning TL, Li L, Parkos CA, Nusrat A (2011) The Wnt antagonist Dkk1 regulates intestinal epithelial homeostasis and wound repair. Gastroenterology 141:259–268CrossRefPubMedPubMedCentral Koch S, Nava P, Addis C, Kim W, Denning TL, Li L, Parkos CA, Nusrat A (2011) The Wnt antagonist Dkk1 regulates intestinal epithelial homeostasis and wound repair. Gastroenterology 141:259–268CrossRefPubMedPubMedCentral
8.
go back to reference Kumar R, Parsad D, Kanwar AJ et al (2011) Altered levels of Ets-1 transcription factor and metalloproteinases in melanocytes from vitiligo patients. Br J Dermatol 165:285–291CrossRefPubMed Kumar R, Parsad D, Kanwar AJ et al (2011) Altered levels of Ets-1 transcription factor and metalloproteinases in melanocytes from vitiligo patients. Br J Dermatol 165:285–291CrossRefPubMed
9.
go back to reference Lei TC, Virador V, Yasumoto K, Vieira WD, Toyofuku K, Hearing VJ (2002) Stimulation of melanoblast pigmentation by 8-methoxypsoralen: the involvement of microphthalmia-associated transcription factor, the protein kinase a signal pathway, and proteasome-mediated degradation. J Invest Dermatol 119(6):1341–1349CrossRefPubMed Lei TC, Virador V, Yasumoto K, Vieira WD, Toyofuku K, Hearing VJ (2002) Stimulation of melanoblast pigmentation by 8-methoxypsoralen: the involvement of microphthalmia-associated transcription factor, the protein kinase a signal pathway, and proteasome-mediated degradation. J Invest Dermatol 119(6):1341–1349CrossRefPubMed
10.
go back to reference Lim YJ, Eunjoo HL, Tong HK, Sang KH, Myung SO, Seong MK, Tae-Jin Y, Chulhun K, Ji-Ho P, Sun YK (2009) Inhibitory effects of arbutin on melanin biosynthesis of α-melanocyte stimulating hormone-induced hyperpigmentation in cultured brownish guinea pig skin tissues. Arch Pharm Res 32(3):367–373CrossRefPubMed Lim YJ, Eunjoo HL, Tong HK, Sang KH, Myung SO, Seong MK, Tae-Jin Y, Chulhun K, Ji-Ho P, Sun YK (2009) Inhibitory effects of arbutin on melanin biosynthesis of α-melanocyte stimulating hormone-induced hyperpigmentation in cultured brownish guinea pig skin tissues. Arch Pharm Res 32(3):367–373CrossRefPubMed
11.
go back to reference Lyros O, Rafiee P, Nie L, Medda R, Jovanovic N, Schmidt J, Mackinnon A, Venu N, Shaker R (2014) Dickkopf 1, the Wnt antagonist, is induced by acidic pH and mediates epithelial cellular senescence in human reflux esophagitis. Am J Physiol Gastrointest Liver Physiol 306:557–574CrossRef Lyros O, Rafiee P, Nie L, Medda R, Jovanovic N, Schmidt J, Mackinnon A, Venu N, Shaker R (2014) Dickkopf 1, the Wnt antagonist, is induced by acidic pH and mediates epithelial cellular senescence in human reflux esophagitis. Am J Physiol Gastrointest Liver Physiol 306:557–574CrossRef
12.
go back to reference Oh SH, Kim JY, Kim MR, Do JE, Shin JY, Hann SK (2012) DKK1 is highly expressed in the dermis of vitiligo lesion: is there association between DKK1 and vitiligo? J Dermatol Sci 66:163–165CrossRefPubMed Oh SH, Kim JY, Kim MR, Do JE, Shin JY, Hann SK (2012) DKK1 is highly expressed in the dermis of vitiligo lesion: is there association between DKK1 and vitiligo? J Dermatol Sci 66:163–165CrossRefPubMed
13.
go back to reference Okazaki M, Yoshimura K, Suzuki Y, Uchida G, Kitano Y et al (2003) The mechanism of epidermal hyperpigmentation in cafe-au-lait macules of neurofibromatosis type 1 (von Recklinghausen’s disease) may be associated with dermal fibroblast-derived stem cell factor and hepatocyte growth factor. Br J Dermatol 148:689–697CrossRefPubMed Okazaki M, Yoshimura K, Suzuki Y, Uchida G, Kitano Y et al (2003) The mechanism of epidermal hyperpigmentation in cafe-au-lait macules of neurofibromatosis type 1 (von Recklinghausen’s disease) may be associated with dermal fibroblast-derived stem cell factor and hepatocyte growth factor. Br J Dermatol 148:689–697CrossRefPubMed
15.
go back to reference Purpura V, Persechino F, Belleudi F, Scrofani C, Raffa S, Persechino S et al (2014) Decreased expression of KGF/FGF7 and its receptor in pathological hypopigmentation. J Cell Mol Med 18:2553–2557CrossRefPubMedPubMedCentral Purpura V, Persechino F, Belleudi F, Scrofani C, Raffa S, Persechino S et al (2014) Decreased expression of KGF/FGF7 and its receptor in pathological hypopigmentation. J Cell Mol Med 18:2553–2557CrossRefPubMedPubMedCentral
16.
go back to reference Rani S, Bhardwaj S, Srivastava N, Sharma VL, Parsad D, Kumar R (2017) Senescence in the lesional fibroblasts of non-segmental vitiligo patients. Arch Dermatol Res 309:123–132CrossRefPubMed Rani S, Bhardwaj S, Srivastava N, Sharma VL, Parsad D, Kumar R (2017) Senescence in the lesional fibroblasts of non-segmental vitiligo patients. Arch Dermatol Res 309:123–132CrossRefPubMed
17.
go back to reference Saito H, Yasumoto K, Takeda K, Takahashi K, Yamamoto H, Shibahara S (2003) Microphthalmia-associated transcription factor in the Wnt signaling pathway. Pigment Cell Res 16:261–265CrossRefPubMed Saito H, Yasumoto K, Takeda K, Takahashi K, Yamamoto H, Shibahara S (2003) Microphthalmia-associated transcription factor in the Wnt signaling pathway. Pigment Cell Res 16:261–265CrossRefPubMed
18.
go back to reference Slominski A, Wortsman J, Plonka PM, Schallreuter KU, Paus R, Tobin DJ (2005) Hair follicle pigmentation. Invest Dermatol 124:13–21CrossRef Slominski A, Wortsman J, Plonka PM, Schallreuter KU, Paus R, Tobin DJ (2005) Hair follicle pigmentation. Invest Dermatol 124:13–21CrossRef
19.
go back to reference Van Amerongen R, Mikels A, Nusse R (2008) Alternative wnt signaling is initiated by distinct receptors. Sci Signal 1:re9PubMed Van Amerongen R, Mikels A, Nusse R (2008) Alternative wnt signaling is initiated by distinct receptors. Sci Signal 1:re9PubMed
20.
go back to reference Walsh NC, Crotti TN, Goldring SR, Gravallese EM (2005) Rheumatic diseases: the effects of inflammation on bone. Immunol Rev 208:228–251CrossRefPubMed Walsh NC, Crotti TN, Goldring SR, Gravallese EM (2005) Rheumatic diseases: the effects of inflammation on bone. Immunol Rev 208:228–251CrossRefPubMed
21.
go back to reference Yamaguchi Y, Hearing VJ (2006) Melanocyte distribution and function in human skin: effects of UV radiation. In: Hearing VJ, Leong SPL. (eds) From melanocytes to malignant melanoma: the progression to malignancy. Humana Press, Totowa, pp 101–115CrossRef Yamaguchi Y, Hearing VJ (2006) Melanocyte distribution and function in human skin: effects of UV radiation. In: Hearing VJ, Leong SPL. (eds) From melanocytes to malignant melanoma: the progression to malignancy. Humana Press, Totowa, pp 101–115CrossRef
22.
go back to reference Yamaguchi Y, Itami S, Watabe H, Yasumoto K, Abdel-Malek ZA, Kubo T et al (2004) Mesenchymal-epithelial interactions in the skin: Increased expression of Dickkopf1 by palmoplantar fibroblasts inhibits melanocyte growth and differentiation. J Cell Biol 165:275–285CrossRefPubMedPubMedCentral Yamaguchi Y, Itami S, Watabe H, Yasumoto K, Abdel-Malek ZA, Kubo T et al (2004) Mesenchymal-epithelial interactions in the skin: Increased expression of Dickkopf1 by palmoplantar fibroblasts inhibits melanocyte growth and differentiation. J Cell Biol 165:275–285CrossRefPubMedPubMedCentral
23.
go back to reference Yamaguchi Y, Morita A, Maeda A, Hearing VJ (2009) Regulation of skin pigmentation and thickness by Dickkopf 1 (DKK1). J Investig Dermatol Symp Proc 14(1):73–75CrossRefPubMedPubMedCentral Yamaguchi Y, Morita A, Maeda A, Hearing VJ (2009) Regulation of skin pigmentation and thickness by Dickkopf 1 (DKK1). J Investig Dermatol Symp Proc 14(1):73–75CrossRefPubMedPubMedCentral
24.
go back to reference Yamaguchi Y, Passeron T, Hoashi T, Watabe H, Rouzaud F, Yasumoto K (2008) Dickkopf 1 (DKK1) regulates skin pigmentation and thickness by affecting Wnt/beta-catenin signaling in keratinocytes. FASEB J 22:1009–1020CrossRefPubMed Yamaguchi Y, Passeron T, Hoashi T, Watabe H, Rouzaud F, Yasumoto K (2008) Dickkopf 1 (DKK1) regulates skin pigmentation and thickness by affecting Wnt/beta-catenin signaling in keratinocytes. FASEB J 22:1009–1020CrossRefPubMed
25.
go back to reference Yamaguchi Y, Passeron T, Watabe H, Yasumoto K, Rouzaud F, Hoashi T (2007) The effects of dickkopf 1 on gene expression and Wnt signaling by melanocytes: Mechanisms underlying its suppression of melanocyte function and proliferation. J Invest Dermatol 127:1217–1225CrossRefPubMed Yamaguchi Y, Passeron T, Watabe H, Yasumoto K, Rouzaud F, Hoashi T (2007) The effects of dickkopf 1 on gene expression and Wnt signaling by melanocytes: Mechanisms underlying its suppression of melanocyte function and proliferation. J Invest Dermatol 127:1217–1225CrossRefPubMed
26.
go back to reference Yamaguchi Y, Takahashi K, Zmudzka BZ, Kornhauser A, Miller SA, Tadokoro T et al (2006) Human skin responses to UV radiation: pigment in the upper epidermis protects against DNA damage in the lower epidermis and facilitates apoptosis. FASEB J 20:1486–1488CrossRefPubMed Yamaguchi Y, Takahashi K, Zmudzka BZ, Kornhauser A, Miller SA, Tadokoro T et al (2006) Human skin responses to UV radiation: pigment in the upper epidermis protects against DNA damage in the lower epidermis and facilitates apoptosis. FASEB J 20:1486–1488CrossRefPubMed
Metadata
Title
Effect of Dickkopf1 on the senescence of melanocytes: in vitro study
Authors
Seema Rani
Rakhee Chauhan
Davinder Parsad
Ravinder Kumar
Publication date
01-05-2018
Publisher
Springer Berlin Heidelberg
Published in
Archives of Dermatological Research / Issue 4/2018
Print ISSN: 0340-3696
Electronic ISSN: 1432-069X
DOI
https://doi.org/10.1007/s00403-018-1820-1

Other articles of this Issue 4/2018

Archives of Dermatological Research 4/2018 Go to the issue