Abstract
It was reported that oral administration of glucosylceramide (GlcCer) from plants ameliorates skin barrier function. GlcCer is a type of glycosphingolipid that exists widely as a component of the cell membrane. However, the mechanism of improvement by dietary GlcCer is not completely understood. The aim of the present study was to investigate the mechanism of GlcCer in the improvement of skin barrier function. Five-week-old male Hos:HR-1 mice were divided into three groups fed on standard diet, unsaturated fatty acids-deficient (HR-AD) diet, and HR-AD diet supplemented with 0.1% P-GlcCer diet. Skin barrier function was evaluated by transepidermal water loss (TEWL) value and wrinkle formation. The effect of transforming growth factor-β (TGF-β) on skin barrier function and collagen content in skin was examined using exogenous TGF-β and its neutralizing antibody. TEWL value and wrinkle formation were decreased by oral administration of pineapple (P)-GlcCer. Not only the TGF-β contents in serum and skin but also hydroxyproline content reduced by the HR-AD diet were restored by P-GlcCer administration. Exogenous TGF-β ameliorated both skin barrier function and collagen contents. However, the improvement of skin barrier function by P-GlcCer was cancelled and collagen content in skin was also decreased by TGF-β antibody injection. Recovery of TGF-β content by P-GlcCer contributed to the production of collagen in skin, resulting in improved skin barrier function.
Similar content being viewed by others
Abbreviations
- AD:
-
Atopic dermatitis
- ECM:
-
Extracellular matrix
- FMOC:
-
9-Fluorenylmethylchloroformate
- GlcCer:
-
Glucosylceramide
- HPLC:
-
High-performance liquid chromatography
- HR-AD:
-
Unsaturated fatty acids-deficient
- OPA:
-
o-Phthalaldehyde
- P-GlcCer:
-
Pineapple glucosylceramide
- PMSF:
-
Phenylmethylsulfonyl fluoride
- SE:
-
Standard error
- TEWL:
-
Transepidermal water loss
- TGF-β:
-
Transforming growth factor-β
- TLR:
-
Toll-like receptor
References
Proksch E, Brandner JM, Jensen JM (2008) The skin: an indispensable barrier. Exp Dermatol 17:1063–1072
Hwang KA, Yi BR, Choi KC (2011) Molecular mechanisms and in vivo mouse models of skin aging associated with dermal matrix alterations. Lab Anim Res 27:1–8
Makrantonaki E, Zouboulis CC (2007) Molecular mechanisms of skin aging: state of the art. Ann NY Acad Sci 1119:40–50
Frantz C, Stewart KM, Weaver VM (2010) The extracellular matrix at a glance. J Cell Sci 123:4195–4200
Jung YR, Lee EK, Kim DH, Park CH, Park MH, Jeong HO, Yokozawa T, Tanaka T, Im DS, Kim ND, Yu BP, Mo SH, Chung HY (2015) Upregulation of collagen expression via PPARβ/δ activation in aged skin by magnesium lithospermate B from Salvia miltiorrhiza. J Nat Prod 78:2110–2115
Ramirez H, Patel SB, Pastar I (2014) The role of TGFβ signaling in wound epithelialization. Adv Wound Care (New Rochelle) 3:482–491
Hwang E, Park SY, Lee HJ, Lee TY, Sun ZW, Yi TH (2014) Gallic acid regulates skin photoaging in UVB-exposed fibroblast and hairless mice. Phytother Res 28:1778–1788
Zambruno G, Marchisio PC, Marconi A, Vaschieri C, Melchiori A, Giannetti A, De Luca M (1995) Transforming growth factor-β1 modulates β1 and β5 integrin receptors and induces the de novo expression of the ανβ6 heterodimer in normal human keratinocytes: implications for wound healing. J Cell Biol 129:853–865
Santoro MM, Gaudino G (2005) Cellular and molecular facets of keratinocyte reepithelization during wound healing. Exp Cell Res 304:274–286
Katsarou A, Armenaka M (2011) Atopic dermatitis in older patients: particular points. J Eur Acad Dermatol Venereol 25:12–18
Elias PM, Hatano Y, Williams ML (2008) Basis for the barrier abnormality in atopic dermatitis: outside–inside–outside pathogenic mechanisms. J Allergy Clin Immunol 121:1337–1343
Jensen JM, Fölster-Holst R, Baranowsky A, Schunck M, Winoto-Morbach S, Neumann C, Schütsze S, Prokch E (2004) Impaired sphingomyelinase activity and epidermal differentiation in atopic dermatitis. J Investig Dermatol 122:1423–1431
Yoshiike T, Aikawa Y, Sindhvananda J, Suto H, Nishimura K, Kawamoto T, Ogawa H (1993) Skin barrier defect in atopic dermatitis: increased permeability of the stratum corneum using dimethyl sulfoxide and theophylline. J Dermatol Sci 5:92–96
Tsuji K, Mitsutake S, Ishikawa J, Takagi Y, Akiyama M, Shimizu H, Tomiyama T, Igarashi Y (2006) Dietary glucosylceramide improves skin barrier function in hairless mice. J Dermatol Sci 44:101–107
van Meer G, Wolthoorn J, Degroote S (2003) The fate and function of glycosphingolipid glucosylceramide. Philos Trans R Soc Lond B Biol Sci 358:869–873
Makiura M, Akamatsu H, Akita H, Yagami A, Shimizu Y, Eiro H, Kuramoto M, Matsunaga K (2004) Atopic dermatitis-like symptoms in HR-1 hairless mice fed a diet low in magnesium and zinc. J Int Med Res 32:392–399
Fujii M, Shimazaki Y, Muto Y, Kohno S, Ohya S, Nabe T (2015) Dietary deficiencies of unsaturated fatty acids and starch cause atopic dermatitis-like pruritus in hairless mice. Exp Dermatol 24:108–113
Kuwata T, Hashimoto T, Ohto N, Kuwahara H, Lee JW, Bamba T, Mizuno M (2017) A metabolite of dietary glucosylceramide from pineapple improves the skin barrier function in hairless mice. J Funct Food 30:228–236
Hutson PR, Crawford ME, Sorkness RL (2003) Liquid chromatographic determination of hydroxyproline in tissue samples. J Chromatogr B 791:427–430
Sumiyoshi K, Nakao A, Ushio H, Mitsuishi K, Okumura K, Tsuboi R, Ra C, Ogawa H (2002) Transforming growth factor-beta1 suppresses atopic dermatitis-like skin lesions in NC/Nga mice. Clin Exp Allergy 32:309–314
Hong J, Buddenkotte J, Berger TG, Steinhoff M (2011) Management of itch in atopic dermatitis. Semin Cutan Med Surg 30:71–86
Seite S, Flores GE, Henley JB, Martin R, Zelenkova H, Aquilar L, Fierer N (2014) Microbiome of affected and unaffected skin of patients with atopic dermatitis before and after emollient treatment. J Drugs Dermatol 13:1365–1372
Ideta R, Sakuta T, Nakano Y, Uchiyama T (2011) Orally administered glucosylceramide improves the skin barrier function by upregulating genes associated with the tight junction and cornified envelope formation. Biosci Biotechnol Biochem 75:1516–1523
Gelse K, Pöschl E, Aigner T (2003) Collagens—structure, function, and biosynthesis. Adv Drug Deliv Rev 55:1531–1546
Egbert M, Ruetz M, Sattler M, Wenck H, Gallinat S, Lucius R, Weise JM (2014) The matricellular protein periostin contributes to proper collagen function and is downregulated during skin aging. J Dermatol Sci 73:40–48
Tiedtke J, Marks O, Morel J (2007) Stimulation of collagen production in human fibroblasts. In: Johnson C (ed) Cosmetic science technolology. Gutenberg Press, Malta, pp 15–18
Sakamoto H, Watanabe K, Koto A, Koizumi G, Satomura T, Watanabe S, Suya S (2015) A bienzyme electrochemical biosensor for the detection of collagen l-hydroxyproline. Sens Biosens Res 4:37–39
Shephard P, Hinz B, Smola-Hess S, Meister JJ, Krieg T, Smloa H (2004) Dissecting the roles of endothelin, TGF-β and GM-CSF on myofibroblast differentiation by keratinocytes. Thromb Haemost 92:262–274
Schmid P, Kunz S, Cerletti N, McMaster G, Cox D (1993) Injury induced expression of TGF-β1 mRNA is enhanced by exogenously applied TGF-βS. Biochem Biophys Res Commun 194:399–406
Yang L, Chan T, Demare J, Iwashina T, Ghahary A, Scott PG, Tredget EE (2001) Healing of burn wounds in transgenic mice overexpressing transforming growth factor-beta 1 in the epidermis. Am J Pathol 159:2147–2157
Suga H, Sugaya M, Fujita H, Asano Y, Tada Y, Kadono T, Sato S (2014) TLR4, rather than TLR2, regulates wound healing through TGF-β and CCL5 expression. J Dermatol Sci 73:117–124
Fischer H, Ellström P, Ekström K, Gustafsson L, Gusstafsson M, Svanborg C (2007) Ceramide as a TLR4 agonist; a putative signaling intermediate between sphingolipid receptors for microbial ligands and TLR4. Cell Microbiol 9:1239–1251
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Compliance with ethics requirements
All animal experiments were approved and treated according to the established rules and the guidelines approved for animal use and care at Kobe University (The Guidelines for the Care and Use of Experimental Animals of Rokkodai Campus, Kobe University) (approval number: 25-06-04).
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Oka, S., Ohto, N., Kuwahara, H. et al. Oral administration of pineapple glucosylceramide improves defective epidermal barrier function by restoring diminished level of TGF-β in the skin. Eur Food Res Technol 246, 867–874 (2020). https://doi.org/10.1007/s00217-020-03454-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00217-020-03454-7