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Reviews in Endocrine and Metabolic Disorders

Erschienen in:

11.10.2016

Beyond acne: Current aspects of sebaceous gland biology and function

verfasst von: Christos C. Zouboulis, Mauro Picardo, Qiang Ju, Ichiro Kurokawa, Dániel Törőcsik, Tamás Bíró, Marlon R. Schneider

Erschienen in: Reviews in Endocrine and Metabolic Disorders | Ausgabe 3/2016

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Abstract

The sebaceous gland is most commonly found in association with a hair follicle. Its traditional function is the holocrine production of sebum, a complex mixture of lipids, cell debris, and other rather poorly characterized substances. Due to the gland’s central role in acne pathogenesis, early research had focused on its lipogenic activity. Less studied aspects of the sebaceous gland, such as stem cell biology, the regulation of cellular differentiation by transcription factors, the significance of specific lipid fractions, the endocrine and specially the neuroendocrine role of the sebaceous gland, and its contribution to the innate immunity, the detoxification of the skin, and skin aging have only recently attracted the attention of researchers from different disciplines. Here, we summarize recent multidisciplinary progress in sebaceous gland research and discuss how sebaceous gland research may stimulate the development of novel therapeutic strategies targeting specific molecular pathways of the pathogenesis of skin diseases.

Zouboulis CC, Tsatsou F. Anatomy of the sebaceous gland. In: Zouboulis CC, Katsambas AD, Kligman AM, editors. Pathogenesis and treatment of acne and rosacea. Berlin: Springer; 2014. p. 27–31.

Schneider MR, Schmidt-Ullrich R, Paus R. The hair follicle as a dynamic miniorgan. Curr Biol. 2009;19:R132–42.PubMedCrossRef

Zouboulis CC, Makrantonaki E. The role of the sebaceous gland. In: Zouboulis CC, Katsambas AD, Kligman AM, editors. Pathogenesis and treatment of acne and rosacea. Berlin: Springer; 2014. p. 77–90.

Schneider MR, Paus R. Sebocytes, multifaceted epithelial cells: lipid production and holocrine secretion. Int J Biochem Cell Biol. 2010;42:181–5.PubMedCrossRef

Zouboulis CC, Baron JM, Bohm M, Kippenberger S, Kurzen H, Reichrath J, et al. Frontiers in sebaceous gland biology and pathology. Exp Dermatol. 2008;17:542–51.PubMedCrossRef

Smith KR, Thiboutot DM. Thematic review series: skin lipids. Sebaceous gland lipids: friend or foe? J Lipid Res. 2008;49:271–81.PubMedCrossRef

Zouboulis CC. Sebaceous gland in human skin—the fantastic future of a skin appendage. J Invest Dermatol. 2003;120:xiv–xv.PubMedCrossRef

Thody AJ, Shuster S. Control and function of sebaceous glands. Physiol Rev. 1989;69:383–416.PubMed

Camera E, Ludovici M, Galante M, Sinagra JL, Picardo M. Comprehensive analysis of the major lipid classes in sebum by rapid resolution high-performance liquid chromatography and electrospray mass spectrometry. J Lipid Res. 2010;51:3377–88.PubMedPubMedCentralCrossRef

10.

Picardo M, Ottaviani M, Camera E, Mastrofrancesco A. Sebaceous gland lipids. Dermatoendocrinol. 2009;1:68–71.PubMedPubMedCentralCrossRef

11.

Pappas A. Epidermal surface lipids. Dermatoendocrinol. 2009;1:72–6.PubMedPubMedCentralCrossRef

12.

Nikkari T. Comparative chemistry of sebum. J Invest Dermatol. 1974;62:257–67.PubMedCrossRef

13.

Ramasastry P, Downing DT, Pochi PE, Strauss JS. Chemical composition of human skin surface lipids from birth to puberty. J Invest Dermatol. 1970;54:139–44.PubMedCrossRef

14.

Zouboulis CC, Schagen S, Alestas T. The sebocyte culture—a model to study the pathophysiology of the sebaceous gland in sebostasis, seborrhoea and acne. Arch Dermatol Res. 2008;300:397–413.PubMedCrossRef

15.

Zouboulis CC, Seltmann H, Neitzel H, Orfanos CE. Establishment and characterization of an immortalized human sebaceous gland cell line (SZ95). J Invest Dermatol. 1999;113:1011–20.PubMedCrossRef

16.

Xia LQ, Zouboulis CC, Detmar M, Mayer-da-Silva A, Stadler R, Orfanos CE. Isolation of human sebaceous glands and cultivation of sebaceous gland-derived cells as an in vitro model. J Invest Dermatol. 1989;93:315–21.PubMedCrossRef

17.

Latham JA, Redfern CP, Thody AJ, De Kretser TA. Immunohistochemical markers of human sebaceous gland differentiation. J Histochem Cytochem. 1989;37:729–34.PubMedCrossRef

18.

Zouboulis CC, Fimmel S, Ortmann J, Turnbull JR, Boschnakow A. Sebaceous glands. In: Hoath SB, Maibach HI, editors. Neonatal skin—structure and function. 2nd ed. New York: Marcel Dekker; 2003. p. 59–88.

19.

Zouboulis CC, Xia L, Akamatsu H, Seltmann H, Fritsch M, Hornemann S, et al. The human sebocyte culture model provides new insights into development and management of seborrhoea and acne. Dermatology. 1998;196:21–31.PubMedCrossRef

20.

Zouboulis CC, Chen W. The sebaceous gland and its role as an endocrine organ. World Clin Dermatol. 2013;1(1):37–51.

21.

Zouboulis CC. Sebaceous gland in human skin—the fantastic future of a skin appendage. J Invest Dermatol. 2003;120:xiv–xv.PubMedCrossRef

22.

Chen W, Obermayer-Pietsch B, Hong JB, Melnik B, Yamasaki O, Dessinioti C, et al. Acne-associated syndromes: models for better understanding of acne pathogenesis. J Eur Acad Dermatol Venereol. 2011;25:637–46.PubMedCrossRef

23.

Zouboulis CC, Nikolakis G, Dessinioti C. Molecular aspects of sebaceous differentiation. In: Zouboulis CC, Katsambas AD, Kligman AM, editors. Pathogenesis and treatment of acne and rosacea. Berlin: Springer; 2014. p. 19–26.

24.

Zouboulis CC. Sebaceous gland receptors. Dermatoendocrinol. 2009;1:77–80.PubMedPubMedCentralCrossRef

25.

Chen W, Zouboulis CC. Hormones and the pilosebaceous unit. Dermatoendocrinol. 2009;1:81–6.PubMedPubMedCentralCrossRef

26.

Wirth H, Gloor M, Stoika D. Sebaceous glands in uninvolved skin of patients suffering from atopic dermatitis. Arch Dermatol Res. 1981;270:167–9.PubMedCrossRef

27.

Shi VY, Leo M, Hassoun L, Chahal DS, Maibach HI, Sivamani RK. Role of sebaceous glands in inflammatory dermatoses. J Am Acad Dermatol. 2015;73:856–63.PubMedCrossRef

28.

Watt FM. The stem cell compartment in human interfollicular epidermis. J Dermatol Sci. 2002;28:173–80.PubMedCrossRef

29.

Niemann C, Owens DM, Hulsken J, Birchmeier W, Watt FM. Expression of DeltaNLef1 in mouse epidermis results in differentiation of hair follicles into squamous epidermal cysts and formation of skin tumours. Development. 2002;129:95–109.PubMed

30.

Merrill BJ, Gat U, DasGupta R, Fuchs E. Tcf3 and Lef1 regulate lineage differentiation of multipotent stem cells in skin. Genes Dev. 2001;15:1688–705.PubMedPubMedCentralCrossRef

31.

Han G, Li AG, Liang YY, Owens P, He W, Lu S, et al. Smad7-induced beta-catenin degradation alters epidermal appendage development. Dev Cell. 2006;11:301–12.PubMedCrossRef

32.

Niemann C, Unden AB, Lyle S, Zouboulis CC, Toftgard R, Watt FM. Indian hedgehog and beta-catenin signaling: role in the sebaceous lineage of normal and neoplastic mammalian epidermis. Proc Natl Acad Sci U S A. 2003;100 suppl 1:11873–80.PubMedPubMedCentralCrossRef

33.

Allen M, Grachtchouk M, Sheng H, Grachtchouk V, Wang A, Wei L, et al. Hedgehog signaling regulates sebaceous gland development. Am J Pathol. 2003;163:2173–8.PubMedPubMedCentralCrossRef

34.

Braun KM, Niemann C, Jensen UB, Sundberg JP, Silva-Vargas V, Watt FM. Manipulation of stem cell proliferation and lineage commitment: visualisation of label-retaining cells in wholemounts of mouse epidermis. Development. 2003;130:5241–55.PubMedCrossRef

35.

Zouboulis CC, Adjaye J, Akamatsu H, Moe-Behrens G, Niemann K. Human skin stem cells and the ageing process. Exp Gerontol. 2008;43:986–97.PubMedCrossRef

36.

Fuchs E, Horsley V. More than one way to skin. Genes Dev. 2008;22:976–85.PubMedPubMedCentralCrossRef

37.

Watt FM, Lo CC, Silva-Vargas V. Epidermal stem cells: an update. Curr Opin Genet Dev. 2006;16:518–24.PubMedCrossRef

38.

Ito M, Liu Y, Yang Z, Nguyen J, Liang F, Morris RJ, et al. Stem cells in the hair follicle bulge contribute to wound repair but not to homeostasis of the epidermis. Nat Med. 2005;11:1351–4.PubMedCrossRef

39.

Selleri S, Seltmann H, Gariboldi S, Shirai YF, Balsari A, Zouboulis CC, et al. Doxorubicin-induced alopecia is associated with sebaceous gland degeneration. J Invest Dermatol. 2006;126:711–20.PubMedCrossRef

40.

Lo Celso C, Berta MA, Braun KM, Frye M, Lyle S, Zouboulis CC, et al. Characterization of bipotential epidermal progenitors derived from human sebaceous gland: contrasting roles of c-Myc and beta-catenin. Stem Cells. 2008;26:1241–52.PubMedCrossRef

41.

Ghazizadeh S, Taichman LB. Multiple classes of stem cells in cutaneous epithelium: a lineage analysis of adult mouse skin. EMBO J. 2001;20:1215–22.PubMedPubMedCentralCrossRef

42.

Horsley V, O’Carroll D, Tooze R, Ohinata Y, Saitou M, Obukhanych T, et al. Blimp1 defines a progenitor population that governs cellular input to the sebaceous gland. Cell. 2006;126:597–609.PubMedPubMedCentralCrossRef

43.

Sellheyer K, Krahl D. Blimp-1: a marker of terminal differentiation but not of sebocytic progenitor cells. J Cutan Pathol. 2010;37:362–70.PubMedCrossRef

44.

Nowak JA, Polak L, Pasolli HA, Fuchs E. Hair follicle stem cells are specified and function in early skin morphogenesis. Cell Stem Cell. 2008;3:33–43.PubMedPubMedCentralCrossRef

45.

Tosti A. A comparison of the histodynamics of sebaceous glands and epidermis in man: a microanatomic and morphometric study. J Invest Dermatol. 1974;62:147–52.PubMedCrossRef

46.

Zouboulis CC, Krieter A, Gollnick H, Mischke D, Orfanos CE. Progressive differentiation of human sebocytes in vitro is characterized by increased cell size and altered antigenic expression and is regulated by culture duration and retinoids. Exp Dermatol. 1994;3:151–60.PubMedCrossRef

47.

Jenkinson DM, Elder HY, Montgomery I, Moss VA. Comparative studies of the ultrastructure of the sebaceous gland. Tissue Cell. 1985;17:683–98.PubMedCrossRef

48.

Thiboutot D, Jabara S, McAllister JM, Sivarajah A, Gilliland K, Cong Z, et al. Human skin is a steroidogenic tissue: steroidogenic enzymes and cofactors are expressed in epidermis, normal sebocytes, and an immortalized sebocyte cell line (SEB-1). J Invest Dermatol. 2003;120:905–14.PubMedCrossRef

49.

Hong I, Lee MH, Na TY, Zouboulis CC, Lee MO. LXRalpha enhances lipid synthesis in SZ95 sebocytes. J Invest Dermatol. 2008;128:1266–72.PubMedCrossRef

50.

Smith TM, Cong Z, Gilliland KL, Clawson GA, Thiboutot DM. Insulin-like growth factor-1 induces lipid production in human SEB-1 sebocytes via sterol response element-binding protein-1. J Invest Dermatol. 2006;126:1226–32.PubMedCrossRef

51.

Ge L, Gordon JS, Hsuan C, Stenn K, Prouty SM. Identification of the delta-6 desaturase of human sebaceous glands: expression and enzyme activity. J Invest Dermatol. 2003;120:707–14.PubMedCrossRef

52.

Zouboulis CC, Jourdan E, Picardo M. Acne is an inflammatory disease and alterations of sebum composition initiate acne lesions. J Eur Acad Dermatol Venereol. 2014;28:527–32.PubMedCrossRef

53.

Pappas A, Anthonavage M, Gordon JS. Metabolic fate and selective utilization of major fatty acids in human sebaceous gland. J Invest Dermatol. 2002;118:164–71.PubMedCrossRef

54.

Robosky LC, Wade K, Woolson D, Baker JD, Manning ML, Gage DA, et al. Quantitative evaluation of sebum lipid components with nuclear magnetic resonance. J Lipid Res. 2008;49:686–92.PubMedCrossRef

55.

Knutson DD. Ultrastructural observations in acne vulgaris: the normal sebaceous follicle and acne lesions. J Invest Dermatol. 1974;62:288–307.PubMedCrossRef

56.

Kurokawa I, Mayer-da-Silva A, Gollnick H, Orfanos CE. Monoclonal antibody labeling for cytokeratins and filaggrin in the human pilosebaceous unit of normal, seborrhoeic and acne skin. J Invest Dermatol. 1988;91:566–71.PubMedCrossRef

57.

Eisen AZ, Holyoke JB, Lobitz Jr WC. Responses of the superficial portion of the human pilosebaceous apparatus to controlled injury. J Invest Dermatol. 1955;25:145–56.PubMedCrossRef

58.

Gu LH, Coulombe PA. Hedgehog signaling, keratin 6 induction, and sebaceous gland morphogenesis: implications for pachyonychia congenita and related conditions. Am J Pathol. 2008;173:752–61.PubMedPubMedCentralCrossRef

59.

Berger J, Moller DE. The mechanisms of action of PPARs. Annu Rev Med. 2002;53:409–35.PubMedCrossRef

60.

Alestas T, Ganceviciene R, Fimmel S, Muller-Decker K, Zouboulis CC. Enzymes involved in the biosynthesis of leukotriene B4 and prostaglandin E2 are active in sebaceous glands. J Mol Med. 2006;84:75–87.PubMedCrossRef

61.

Chen W, Yang CC, Sheu HM, Seltmann H, Zouboulis CC. Expression of peroxisome proliferator-activated receptor and CCAAT/enhancer binding protein transcription factors in cultured human sebocytes. J Invest Dermatol. 2003;121:441–7.PubMedCrossRef

62.

Dozsa A, Dezso B, Toth BI, Bacsi A, Poliska S, Camera E, et al. PPARγ nuclear receptor coupled arachidonic acid signaling is involved in differentiation and lipid production of human sebocytes. J Invest Dermatol. 2014;134:910–20.PubMedCrossRef

63.

Wróbel A, Seltmann H, Fimmel S, Muller-Decker K, Tsukada M, Bogdanoff B, et al. Differentiation and apoptosis in human immortalized sebocytes. J Invest Dermatol. 2003;120:175–81.PubMedCrossRef

64.

Trivedi NR, Cong Z, Nelson AM, Albert AJ, Rosamilia LL, Sivarajah S, et al. Peroxisome proliferator-activated receptors increase human sebum production. J Invest Dermatol. 2006;126:2002–9.PubMedCrossRef

65.

Zouboulis CC, Nestoris S, Adler YD, Orth M, Orfanos CE, Picardo M, et al. A new concept for acne therapy: a pilot study with zileuton, an oral 5-lipoxygenase inhibitor. Arch Dermatol. 2003;139:668–70.PubMedCrossRef

66.

Zouboulis CC, Seltmann H, Alestas T. Zileuton prevents the activation of the leukotriene pathway and reduces sebaceous lipogenesis. Exp Dermatol. 2010;19:148–50.PubMedCrossRef

67.

Schuster M, Zouboulis CC, Ochsendorf F, Muller J, Thaci D, Bernd A, et al. Peroxisome proliferator-activated receptor activators protect sebocytes from apoptosis: a new treatment modality for acne? Br J Dermatol. 2011;164:182–6.PubMedCrossRef

68.

Zouboulis CC. The human skin as a hormone target and an endocrine gland. Hormones (Athens). 2004;3:9–26.CrossRef

69.

Russell LE, Harrison WJ, Bahta AW, Zouboulis CC, Burrin JM, Philpott MP. Characterization of liver X receptor expression and function in human skin and the pilosebaceous unit. Exp Dermatol. 2007;16:844–52.PubMedCrossRef

70.

Gross DN, van den Heuvel AP, Birnbaum MJ. The role of FoxO in the regulation of metabolism. Oncogene. 2008;27:2320–36.PubMedCrossRef

71.

Mirdamadi Y, Thielitz A, Wiede A, Goihl A, Papakonstantinou E, Hartig R, et al. Insulin and insulin-like growth factor-1 can modulate the phosphoinositide-3-kinase/Akt/FoxO1 pathway in SZ95 sebocytes in vitro. Mol Cell Endocrinol. 2015;415:32–44.PubMedCrossRef

72.

Melnik B, Zouboulis CC. Potential role of FoxO1 and mTORC1 in the pathogenesis of Western diet-induced acne. Exp Dermatol. 2013;22:311–5.PubMedPubMedCentralCrossRef

73.

Pelle E, McCarthy J, Seltmann H, Huang X, Mammone T, Zouboulis CC, et al. Identification of histamine receptors and reduction of squalene levels by an antihistamine in sebocytes. J Invest Dermatol. 2008;128:1280–5.PubMedCrossRef

74.

Zouboulis CC. Sebaceous gland receptors. Dermatoendocrinol. 2009;1:77–80.PubMedPubMedCentralCrossRef

75.

Tsukada M, Schroder M, Roos TC, Chandraratna RA, Reichert U, Merk HF, et al. 13-cis retinoic acid exerts its specific activity on human sebocytes through selective intracellular isomerization to all-trans retinoic acid and binding to retinoid acid receptors. J Invest Dermatol. 2000;115:321–7.PubMedCrossRef

76.

Zouboulis CC, Korge B, Akamatsu H, Xia LQ, Schiller S, Gollnick H, et al. Effects of 13-cis-retinoic acid, all-trans-retinoic acid, and acitretin on the proliferation, lipid synthesis and keratin expression of cultured human sebocytes in vitro. J Invest Dermatol. 1991;96:792–7.PubMedCrossRef

77.

Kim MJ, Deplewski D, Ciletti N, Michel S, Reichert U, Rosenfield RL. Limited cooperation between peroxisome proliferator-activated receptors and retinoid X receptor agonists in sebocyte growth and development. Mol Genet Metab. 2001;74:362–9.PubMedCrossRef

78.

Dahlhoff M, Camera E, Picardo M, Zouboulis CC, Chan L, Chang BH, et al. PLIN2, the major perilipin regulated during sebocyte differentiation, controls sebaceous lipid accumulation in vitro and sebaceous gland size in vivo. Biochim Biophys Acta Gen Subjects. 1830;2013:4642–9.

79.

Camera E, Dahlhoff M, Ludovici N, Zouboulis CC, Schneider M. Perilipin 3 modulates specific lipogenic pathways in SZ95 sebocytes. Exp Dermatol. 2014;23:759–61.PubMedCrossRef

80.

Dahlhoff M, Camera E, Picardo M, Zouboulis CC, Schneider MR. Angiopoietin-like 4, a protein strongly induced during sebocyte differentiation, regulates sebaceous lipogenesis but is dispensable for sebaceous gland function in vivo. J Dermatol Sci. 2014;75:148–50.PubMedCrossRef

81.

Fritsch M, Orfanos CE, Zouboulis CC. Sebocytes are the key regulators of androgen homeostasis in human skin. J Invest Dermatol. 2001;116:793–800.PubMedCrossRef

82.

Chen W, Zouboulis CC, Fritsch M, Kodelja V, Orfanos CE. Heterogeneity and quantitative differences of type 1 5alpha-reductase expression in cultured skin epithelial cells. Dermatology. 1998;196:51–2.PubMedCrossRef

83.

Fimmel S, Saborowski A, Terouanne B, Sultan C, Zouboulis CC. Inhibition of the androgen receptor by antisense oligonucleotides regulates the biological activity of androgens in SZ95 sebocytes. Horm Metab Res. 2007;39:149–56.PubMedCrossRef

84.

Akamatsu H, Zouboulis CC, Orfanos CE. Spironolactone directly inhibits proliferation of cultured human facial sebocytes and acts antagonistically to testosterone and 5alpha-dihydrotestosterone in vitro. J Invest Dermatol. 1993;100:660–2.PubMedCrossRef

85.

Rosenfield RL, Deplewski D, Kentsis A, Ciletti N. Mechanisms of androgen induction of sebocyte differentiation. Dermatology. 1998;196:43–6.PubMedCrossRef

86.

Makrantonaki E, Zouboulis CC. Testosterone metabolism to 5alpha-dihydrotestosterone and synthesis of sebaceous lipids is regulated by the peroxisome proliferator-activated receptor ligand linoleic acid in human sebocytes. Br J Dermatol. 2007;156:428–32.PubMedCrossRef

87.

Heemers HV, Tindall DJ. Androgen receptor (AR) coregulators: a diversity of functions converging on and regulating the AR transcriptional complex. Endocr Rev. 2007;28:778–808.PubMedCrossRef

88.

Borlu M, Karaca Z, Yildiz H, Tanriverdi F, Demirel B, Elbuken G, et al. Acromegaly is associated with decreased skin transepidermal water loss and temperature, and increased skin pH and sebum secretion partially reversible after treatment. Growth Horm IGF Res. 2012;22:82–6.

89.

Deplewski D, Rosenfield RL. Role of hormones in pilosebaceous unit development. Endocr Rev. 2000;21:363–92.PubMedCrossRef

90.

Cappel M, Mauger D, Thiboutot D. Correlation between serum levels of insulin-like growth factor 1, dehydroepiandrosterone sulfate, and dihydrotestosterone and acne lesion counts in adult women. Arch Dermatol. 2005;141:333–8.PubMedCrossRef

91.

Makrantonaki E, Vogel K, Fimmel S, Oeff M, Seltmann H, Zouboulis CC. Interplay of IGF-I and 17beta-estradiol at age-specific levels in human sebocytes and fibroblasts in vitro. Exp Gerontol. 2008;43:939–46.PubMedCrossRef

92.

Deplewski D, Rosenfield RL. Growth hormone and insulin-like growth factors have different effects on sebaceous cell growth and differentiation. Endocrinology. 1999;140:4089–94.PubMed

93.

Smith TM, Gilliland K, Clawson GA, Thiboutot D. IGF-1 induces SREBP-1 expression and lipogenesis in SEB-1 sebocytes via activation of the phosphoinositide 3-kinase/Akt pathway. J Invest Dermatol. 2008;128:1286–93.PubMedCrossRef

94.

Melnik BC. Role of FGFR2-signaling in the pathogenesis of acne. Dermatoendocrinol. 2009;1:141–56.PubMedPubMedCentralCrossRef

95.

Melnik BC, Vakilzadeh F, Aslanidis C, Schmitz G. Unilateral segmental acneiform naevus: a model disorder towards understanding fibroblast growth factor receptor 2 function in acne? Br J Dermatol. 2008;158:1397–9.PubMedCrossRef

96.

Grose R, Fantl V, Werner S, Chioni AM, Jarosz M, Rudling R, et al. The role of fibroblast growth factor receptor 2b in skin homeostasis and cancer development. EMBO J. 2007;26:1268–78.PubMedPubMedCentralCrossRef

97.

Melnik BC, Schmitz G, Zouboulis CC. Anti-acne agents attenuate FGFR2 signal transduction in acne. J Invest Dermatol. 2009;129:1868–77.PubMedCrossRef

98.

Schneider MR, Samborski A, Bauersachs S, Zouboulis CC. Differentially regulated microRNAs during human sebaceous lipogenesis. J Dermatol Sci. 2013;70:88–93.PubMedCrossRef

99.

Tetzlaff MT, Curry JL, Yin V, Pattanaprichakul P, Manonukul J, Uiprasertkul M, et al. Distinct pathways in the pathogenesis of sebaceous carcinomas implicated by differentially expressed microRNAs. JAMA Ophthalmol. 2015;133:1109–16.PubMedCrossRef

100.

Montagna W, Parakkal PF. The structure and function of the skin. London: Academic Press; 1974.

101.

Montagna W, Kligman AM, Carlisle KS. Atlas of normal human skin. Heidelberg: Springer; 1992.CrossRef

102.

Toyoda M, Nakamura M, Makino T, Kagoura M, Morohashi M. Sebaceous glands in acne patients express high levels of neutral endopeptidase. Exp Dermatol. 2002;11:241–7.PubMedCrossRef

103.

Ganceviciene R, Graziene V, Fimmel S, Zouboulis CC. Involvement of the corticotropin-releasing hormone system in the pathogenesis of acne vulgaris. Br J Dermatol. 2009;160:345–52.PubMedCrossRef

104.

Zouboulis CC, Seltmann H, Hiroi N, Chen W, Young M, Oeff M, et al. Corticotropin-releasing hormone: an autocrine hormone that promotes lipogenesis in human sebocytes. Proc Natl Acad Sci U S A. 2002;99:7148–53.PubMedPubMedCentralCrossRef

105.

Krause K, Schnitger A, Fimmel S, Glass E, Zouboulis CC. Corticotropin-releasing hormone skin signaling is receptor-mediated and is predominant in the sebaceous glands. Horm Metab Res. 2007;39:166–70.PubMedCrossRef

106.

Lipton JM, Catania A. Anti-inflammatory actions of the neuroimmunomodulator alpha-MSH. Immunol Today. 1997;18:140–5.PubMedCrossRef

107.

Bohm M, Schiller M, Stander S, Seltmann H, Li Z, Brzoska T, et al. Evidence for expression of melanocortin-1 receptor in human sebocytes in vitro and in situ. J Invest Dermatol. 2002;118:533–9.PubMedCrossRef

108.

Ganceviciene R, Graziene V, Bohm M, Zouboulis CC. Increased in situ expression of melanocortin-1 receptor in sebaceous glands of lesional skin of patients with acne vulgaris. Exp Dermatol. 2007;16:547–52.PubMedCrossRef

109.

Zhang L, Li WH, Anthonavage M, Eisinger M. Melanocortin-5 receptor: a marker of human sebocyte differentiation. Peptides. 2006;27:413–20.PubMedCrossRef

110.

Maresca V, Flori E, Camera E, Bellei B, Aspite N, Ludovici M, et al. Linking αMSH with PPARγ in B16-F10 melanoma. Pigment Cell Melanoma Res. 2013;26:113–27.PubMedCrossRef

111.

Abdel-Naser MB, Seltmann H, Zouboulis CC. SZ95 sebocytes induce epidermal melanocyte dendricity and proliferation in vitro. Exp Dermatol. 2012;21:393–5.PubMedCrossRef

112.

Maresca V, Flori E, Picardo M. Skin phototype: a new perspective. Pigment Cell Melanoma Res. 2015;28:378–89.PubMedCrossRef

113.

Stander S, Schmelz M, Metze D, Luger T, Rukwied R. Distribution of cannabinoid receptor 1 (CB1) and 2 (CB2) on sensory nerve fibers and adnexal structures in human skin. J Dermatol Sci. 2005;38:177–88.PubMedCrossRef

114.

Dobrosi N, Toth BI, Nagy G, Dozsa A, Geczy T, Nagy L, et al. Endocannabinoids enhance lipid synthesis and apoptosis of human sebocytes via cannabinoid receptor-2-mediated signaling. FASEB J. 2008;22:3685–95.PubMedCrossRef

115.

Toyoda M, Nakamura M, Morohashi M. Neuropeptides and sebaceous glands. Eur J Dermatol. 2001;12:422–7.

116.

Ansorge S, Reinhold D, Lendeckel U. Propolis and some of its constituents down-regulate DNA synthesis and inflammatory cytokine production but induce TGF-beta1 production of human immune cells. Z Naturforsch C. 2003;58:580–9.PubMedCrossRef

117.

Thielitz A, Reinhold D, Vetter R, Bank U, Helmuth M, Hartig R, et al. Inhibitors of dipeptidyl peptidase IV and aminopeptidase N target major pathogenetic steps in acne initiation. J Invest Dermatol. 2007;127:1042–51.PubMedCrossRef

118.

Braff MH, Bardan A, Nizet V, Gallo RL. Cutaneous defense mechanisms by antimicrobial peptides. J Invest Dermratol. 2005;125:9–13.CrossRef

119.

Lee DY, Yamasaki K, Rudsil J, Zouboulis CC, Park GT, Yang JM, et al. Sebocytes express functional cathelicidin antimicrobial peptides and can act to kill Propionibacterium acnes. J Invest Dermatol. 2008;128:1863–6.PubMedPubMedCentralCrossRef

120.

Dahlhoff M, Zouboulis CC, Schneider MR. Expression of dermcidin in sebocytes supports a role for sebum in the constitutive innate defense of human skin. J Dermatol Sci. 2016;81:124–6.PubMedCrossRef

121.

Chronnell CM, Ghali LR, Ali RS, Quinn AG, Holland DB, Bull JJ, et al. Human beta defensin-1 and -2 expression in human pilosebaceous units: upregulation in acne vulgaris lesions. J Invest Dermatol. 2001;117:1120–5.PubMedCrossRef

122.

Nagy I, Pivarcsi A, Koreck A, Szell M, Urban E, Kemeny L. Distinct strains of Propionibacterium acnes induce selective human beta-defensin-2 and interleukin-8 expression in human keratinocytes through toll-like receptors. J Invest Dermatol. 2005;124:931–8.PubMedCrossRef

123.

Nakatsuji T, Kao MC, Zhang L, Zouboulis CC, Gallo RL, Huang CM. Sebum free fatty acids enhance the innate immune defense of human sebocytes by upregulating beta-defensin-2 expression. J Invest Dermatol. 2010;130:985–94.PubMedCrossRef

124.

Georgel P, Crozat K, Lauth X, Makrantonaki E, Seltmann H, Sovath S, et al. A toll-like receptor 2-responsive lipid effector pathway protects mammals against skin infections with gram-positive bacteria. Infect Immun. 2005;73:4512–21.PubMedPubMedCentralCrossRef

125.

Lee DY, Huang CM, Nakatsuji T, Thiboutot D, Kang SA, Monestier M, et al. Histone H4 is a major component of the antimicrobial action of human sebocytes. J Invest Dermatol. 2009;129:2489–96.PubMedPubMedCentralCrossRef

126.

Nakatsuji T, Kao MC, Fang J-Y, Zouboulis CC, Zhang L, Gallo RL, et al. Antimicrobial property of lauric acid against Propionibacterium acnes: its therapeutic potential for inflammatory acne vulgaris. J Invest Dermatol. 2009;129:2480–8.PubMedPubMedCentralCrossRef

127.

Drake DR, Brogden KA, Dawson DV, Wertz PW. Thematic review series: skin lipids. Antimicrobial lipids at the skin surface. J Lipid Res. 2008;49:4–11.PubMedCrossRef

128.

Wille JJ, Kydonieus A. Palmitoleic acid isomer (C16:1delta6) in human skin sebum is effective against gram-positive bacteria. Skin Pharmacol Appl Skin Physiol. 2003;16:176–87.PubMedCrossRef

129.

Zouboulis CC, Angres S, Seltmann H. Regulation of stearoyl-CoA desaturase and fatty acid desaturase 2 expression by linoleic acid and arachidonic acid in human sebocytes leads to enhancement of proinflammatory activity but does not affect lipogenesis. Br J Dermatol. 2011;165:269–76.PubMedCrossRef

130.

Kovács D, Lovászi M, Póliska S, Oláh A, Bíró T, Veres I, et al. Sebocytes differentially express and secrete adipokines. Exp Dermatol. 2016;25:194–9.PubMedCrossRef

131.

Chen HC, Smith SJ, Tow B, Elias PM, Farese Jr RV. Leptin modulates the effects of acyl CoA:diacylglycerol acyltransferase deficiency on murine fur and sebaceous glands. J Clin Invest. 2002;109:175–81.PubMedPubMedCentralCrossRef

132.

Töröcsik D, Kovács D, Camera E, Lovászi M, Cseri K, Nagy GG, et al. Leptin promotes a pro-inflammtory lipid profile and induces inflammatory pathways in human SZ95 sebocytes. Br J Dermatol. 2014;171:1326–35.PubMedCrossRef

133.

Lee SH, Jeong SK, Ahn SK. An update of the defensive barrier function of skin. Yonsei Med J. 2006;47:293–306.PubMedPubMedCentralCrossRef

134.

Masaki H. Role of antioxidants in the skin: anti-aging effects. J Dermatol Sci. 2010;58:85–90.PubMedCrossRef

135.

De Luca C, Valacchi G. Surface lipids as multifunctional mediators of skin responses to environmental stimuli. Mediators Inflamm. 2010;2010:321494.PubMedPubMedCentral

136.

Briganti S, Picardo M. Antioxidant activity, lipid peroxidation and skin diseases. What’s new. J Eur Acad Dermatol Venereol. 2003;17:663–9.PubMedCrossRef

137.

Ekanayake-Mudiyanselage S, Thiele J. Die Talgdrüse als transporter für vitamin E. Hautarzt. 2006;57:291–6.PubMedCrossRef

138.

Lefebvre MA, Pham DM, Boussouira B, Qiu H, Ye C, Long X, et al. Consequences of urban pollution upon skin status. A controlled study in Shanghai area Int J Cosmet Sci. 2015;38(3):217–23.PubMedCrossRef

139.

Pham DM, Boussouira B, Moyal D, Nguyen QL. Oxidization of squalene, a human skin lipid: a new and reliable marker of environmental pollution studies. Int J Cosmet Sci. 2015;37:357–65.PubMedCrossRef

140.

Panteleyev AA, Bickers DR. Dioxin-induced chloracne—reconstructing the cellular and molecular mechanisms of a classic environmental disease. Exp Dermatol. 2006;15:705–30.PubMedCrossRef

141.

Kamp S, Fiehn AM, Stenderup K, Rosada C, Pakkenberg B, Kemp K, et al. Hidradenitis suppurativa: a disease of the absent sebaceous gland? Sebaceous gland number and volume are significantly reduced in uninvolved hair follicles from patients with hidradenitis suppurativa. Br J Dermatol. 2011;164:1017–22.PubMedCrossRef

142.

Ju Q, Fimmel S, Hinz N, Stahlmann R, Xia L, Zouboulis CC. 2,3,7,8-Tetrachlorodibenzo-p-dioxin alters sebaceous gland cell differentiation in vitro. Exp Dermatol. 2011;20:320–5.PubMedCrossRef

143.

Hu T, Pan Z, Yu Q, Mo X, Song N, Yan M, et al. Benzo(a)pyrene induces interleukin (IL)-6 production and reduces lipid synthesis in human SZ95 sebocytes via the aryl hydrocarbon receptor signaling pathway. Environ Toxicol Pharmacol. 2016;43:54–60.PubMedCrossRef

144.

Esser C. Biology and function of the aryl hydrocarbon receptor: report of an international and interdisciplinary conference. Arch Toxicol. 2012;86:1323–9.PubMedCrossRef

145.

Ju Q, Yu Q, Song NJ, Tan Y, Xia LQ, Zouboulis CC. Expression of aryl hydrocarbon receptor in human epidermis, hair follicles and sebaceous glands and its significance. Chin J Dermatol. 2011;44:761–4.

146.

Rowe JM, Welsh C, Pena RN, Wolf CR, Brown K, Whitelaw CB. Illuminating role of CYP1A1 in skin function. J Invest Dermatol. 2008;128:1866–8.PubMedCrossRef

147.

Paraskevaidis A, Drakoulis N, Roots I, Orfanos CE, Zouboulis CC. Polymorphisms in the human cytochrome P-450 1A1 gene (CYP1A1) as a factor for developing acne. Dermatololgy. 1998;196:171–5.CrossRef

148.

Nikolakis G, Seltmann H, Hossini A, Makrantonaki E, Knolle J, Zouboulis CC. Ex vivo human skin and SZ95 sebocytes exhibit a homeostatic interaction in a novel co-culture contact model. Exp Dermatol. 2015;24:497–502.PubMedCrossRef

149.

Zheng Y, Eilertsen KJ, Ge L, Zhang L, Sundberg JP, Prouty SM, et al. Scd1 is expressed in sebaceous glands and is disrupted in the asebia mouse. Nat Genet. 1999;23:268–70.PubMedCrossRef

150.

Dahlhoff M, Camera E, Schäfer M, Emrich D, Riethmache D, Foster E, et al. Sebaceous lipids are essential for water repulsion, protection against UVB-induced apoptosis, and ocular integrity in mice. Development. 2016;143(10):1823–31.PubMedCrossRef

151.

Stenn KS, Zheng Y, Parimoo S. Phylogeny of the hair follicle: the sebogenic hypothesis. J Invest Dermatol. 2008;128:1576–8.PubMedCrossRef

152.

Dahlhoff M, Fröhlich T, Arnold GJ, Müller U, Leonhardt H, Zouboulis CC, et al. Characterization of the sebocyte lipid droplet proteome reveals novel potential regulators of sebaceous lipogenesis. Exp Cell Res. 2015;332:146–55.PubMedCrossRef

153.

Dahlhoff M, Fröhlich T, Arnold GJ, Zouboulis CC, Schneider NR. LC-MS/MS analysis reveals a broad functional spectrum of proteins in the secretome of sebocytes. Exp Dermatol. 2016;25:66–7.PubMedCrossRef

154.

Magnusdottir E, Kalachikov S, Mizukoshi K, Savitsky D, Ishida-Yamamoto A, Panteleyev AA, et al. Epidermal terminal differentiation depends on B lymphocyte-induced maturation protein-1. Proc Natl Acad Sci U S A. 2007;104:14988–93.PubMedPubMedCentralCrossRef

155.

Karnik P, Tekeste Z, McCormick TS, Gilliam AC, Price VH, Cooper KD, et al. Hair follicle stem cell-specific PPARgamma deletion causes scarring alopecia. J Invest Dermatol. 2009;129:1243–57.PubMedCrossRef

156.

Miyazaki M, Man WC, Ntambi JM. Targeted disruption of stearoyl-CoA desaturase1 gene in mice causes atrophy of sebaceous and meibomian glands and depletion of wax esters in the eyelid. J Nutr. 2001;131:2260–8.PubMed

157.

Jong MC, Gijbels MJ, Dahlmans VE, Gorp PJ, Koopman SJ, Ponec M, et al. Hyperlipidemia and cutaneous abnormalities in transgenic mice overexpressing human apolipoprotein C1. J Clin Invest. 1998;101:145–52.PubMedPubMedCentralCrossRef

158.

Arnold I, Watt FM. c-Myc activation in transgenic mouse epidermis results in mobilization of stem cells and differentiation of their progeny. Curr Biol. 2001;11:558–68.PubMedCrossRef

159.

Waikel RL, Kawachi Y, Waikel PA, Wang XJ, Roop DR. Deregulated expression of c-Myc depletes epidermal stem cells. Nat Genet. 2001;28:165–8.PubMedCrossRef

160.

Neufang G, Furstenberger G, Heidt M, Marks F, Muller-Decker K. Abnormal differentiation of epidermis in transgenic mice constitutively expressing cyclooxygenase-2 in skin. Proc Natl Acad Sci U S A. 2001;98:7629–34.PubMedPubMedCentralCrossRef

161.

Dahlhoff M, Muller AK, Wolf E, Werner S, Schneider MR. Epigen transgenic mice develop enlarged sebaceous glands. J Invest Dermatol. 2010;130:623–6.PubMedCrossRef

Titel: Beyond acne: Current aspects of sebaceous gland biology and function
verfasst von: Christos C. Zouboulis
Mauro Picardo
Qiang Ju
Ichiro Kurokawa
Dániel Törőcsik
Tamás Bíró
Marlon R. Schneider
Publikationsdatum: 11.10.2016
Verlag: Springer US
Erschienen in: Reviews in Endocrine and Metabolic Disorders / Ausgabe 3/2016
Print ISSN: 1389-9155
Elektronische ISSN: 1573-2606
DOI: https://doi.org/10.1007/s11154-016-9389-5

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Beyond acne: Current aspects of sebaceous gland biology and function

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