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01.10.2005 | Current Opinion

Peroxisome Proliferator-Activated Receptors and their Ligands

Entry Into the Post-Glucocorticoid Era of Skin Treatment?

verfasst von: Günther Weindl, Monika Schäfer-Korting, Martin Schaller, Hans Christian Korting

Erschienen in: Drugs | Ausgabe 14/2005

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Abstract

Glucocorticoids have remained one of the most frequently used classes of drugs for the treatment of skin diseases since their introduction more than 50 years ago. As a result of the discovery of new members of the nuclear hormone receptor (NR) superfamily, alternative therapeutic interventions that target retinoid and vitamin D receptors have been developed. Peroxisome proliferator-activated receptors (PPARs) comprise another important NR subfamily, consisting of three different isotypes: PPARα, PPARδ (PPARβ) and PPARγ. These NRs are activated by a variety of natural and synthetic ligands such as fatty acids, eicosanoids, and antidiabetic and antihyperlipidaemic agents. While these receptors are established as regulators of gene expression in lipid and glucose homeostasis, evidence is now accumulating that PPARs also play a crucial role in cutaneous biology. Results from in vitro and in vivo studies have indicated the involvement of PPARs in epidermal maturation, proliferation and differentiation, as well as in immune and inflammatory responses, carcinogenesis, hyperpigmentation and skin wound healing. Furthermore, treatment of psoriatic patients with PPARγ activators (thiazolidinediones) has been shown to induce beneficial effects. However, the effects of PPAR ligands should be carefully evaluated to determine whether they are in fact mediated via PPAR-dependent mechanisms. Nonetheless, PPARs seem to have significant potential as therapeutic targets in skin inflammatory disorders.

Brazzini B, Pimpinelli N. New and established topical cortico-steroids in dermatology: clinical pharmacology and therapeutic use. Am J Clin Dermatol 2002; 3(1): 47–58PubMedCrossRef

Sivaramakrishnan R, Nakamura C, Mehnert W, et al. Glucocor-ticoid entrapment into lipid carriers: characterisation by parelectric spectroscopy and influence on dermal uptake. J Control Release 2004 Jul 7; 97(3): 493–502PubMed

Schafer-Korting M, Kleuser B, Ahmed M, et al. Glucocorticoids for human skin: new aspects of the mechanism of action. Skin Pharmacol Physiol 2005 May; 18(3): 103–14PubMedCrossRef

Nettles KW, Greene GL. Ligand control of coregulator recruitment to nuclear receptors. Annu Rev Physiol 2005; 67: 309–33PubMedCrossRef

Gronemeyer H, Gustafsson JA, Laudet V. Principles for modulation of the nuclear receptor superfamily. Nat Rev Drug Discov 2004 Nov; 3(11): 950–64PubMedCrossRef

Issemann I, Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 1990 Oct 18; 347(6294): 645–50PubMedCrossRef

Schmidt A, Endo N, Rutledge SJ, et al. Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids. Mol Endocrinol 1992 Oct; 6(10): 1634–41PubMedCrossRef

Dreyer C, Krey G, Keller H, et al. Control of the peroxisomal beta-oxidation pathway by a novel family of nuclear hormone receptors. Cell 1992 Mar 6; 68(5): 879–87PubMedCrossRef

Mukherjee R, Jow L, Croston GE, et al. Identification, characterization, and tissue distribution of human peroxisome proliferator-activated receptor (PPAR) isoforms PPARgam-ma2 versus PPARgammal and activation with retinoid X receptor agonists and antagonists. J Biol Chem 1997 Mar 21; 272(12): 8071–6PubMedCrossRef

10.

Nuclear Receptors Nomenclature Committee. A unified nomenclature system for the nuclear receptor superfamily. Cell 1999 Apr 16; 97(2): 161–3CrossRef

11.

Xu HE, Lambert MH, Montana VG, et al. Structural determinants of ligand binding selectivity between the peroxisome proliferator-activated receptors. Proc Natl Acad Sci U S A 2001 Nov 20; 98(24): 13919–24PubMedCrossRef

12.

Nomura M, Tanase T, Ide T, et al. Design, synthesis, and evaluation of substituted phenylpropanoic acid derivatives as human peroxisome proliferator activated receptor activators. Discovery of potent and human peroxisome proliferator activated receptor alpha subtype-selective activators. J Med Chem 2003 Aug 14; 46(17): 3581–99

13.

Berger JP, Petro AE, Macnaul KL, et al. Distinct properties and advantages of a novel peroxisome proliferator-activated protein γ selective modulator. Mol Endocrinol 2003 Apr; 17(4): 662–76PubMedCrossRef

14.

Sznaidman ML, Haffner CD, Maloney PR, et al. Novel selective small molecule agonists for peroxisome proliferator-activated receptor delta (PPARdelta): synthesis and biological activity. Bioorg Med Chem Lett 2003 May 5; 13(9): 1517–21PubMedCrossRef

15.

Shearer BG, Hoekstra WJ. Recent advances in peroxisome proliferator-activated receptor science. Curr Med Chem 2003 Feb; 10(4): 267–80PubMedCrossRef

16.

Gottlicher M, Widmark E, Li Q, et al. Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor. Proc Natl Acad Sci U S A 1992 May 15; 89(10): 4653–7PubMedCrossRef

17.

Keller H, Dreyer C, Medin J, et al. Fatty acids and retinoids control lipid metabolism through activation of peroxisome proliferator-activated receptor-retinoid X receptor heterodimers. Proc Natl Acad Sci U S A 1993 Mar 15; 90(6): 2160–4PubMedCrossRef

18.

Xu HE, Lambert MH, Montana VG, et al. Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol Cell 1999 Mar; 3(3): 397–403PubMedCrossRef

19.

Devchand PR, Keller H, Peters JM, et al. The PPARa-leuko-triene B4 pathway to inflammation control. Nature 1996 Nov 7; 384(6604): 39–43PubMedCrossRef

20.

Kliewer SA, Sundseth SS, Jones SA, et al. Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. Proc Natl Acad Sci U S A 1997 Apr 29; 94(9): 4318–23PubMedCrossRef

21.

Yu K, Bayona W, Kallen CB, et al. Differential activation of peroxisome proliferator-activated receptors by eicosanoids. J Biol Chem 1995 Oct 13; 270(41): 23975–83PubMedCrossRef

22.

Forman BM, Chen J, Evans RM. Hypolipidemic drugs, polyun-saturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta. Proc Natl Acad Sci U S A 1997 Apr 29; 94(9): 4312–7PubMedCrossRef

23.

Oliver Jr WR, Shenk JL, Snaith MR, et al. A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport. Proc Natl Acad Sci U S A 2001 Apr 24; 98(9): 5306–11PubMedCrossRef

24.

Berger J, Leibowitz MD, Doebber TW, et al. Novel peroxisome proliferator-activated receptor (PPAR) gamma and PPARdelta ligands produce distinct biological effects. J Biol Chem 1999 Mar 5; 274(10): 6718–25PubMedCrossRef

25.

Kliewer SA, Lenhard JM, Willson TM, et al. A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation. Cell 1995 Dec 1; 83(5): 813–9PubMedCrossRef

26.

Forman BM, Tontonoz P, Chen J, et al. 15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma. Cell 1995 Dec 1; 83(5): 803–12PubMedCrossRef

27.

Nagy L, Tontonoz P, Alvarez JG, et al. Oxidized LDL regulates macrophage gene expression through ligand activation of PPARγ. Cell 1998 Apr 17; 93(2): 229–40PubMedCrossRef

28.

Lehmann JM, Moore LB, Smith-Oliver TA, et al. An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). J Biol Chem 1995 Jun 2; 270(22): 12953–6PubMedCrossRef

29.

Lehmann JM, Lenhard JM, Oliver BB, et al. Peroxisome proliferator-activated receptors alpha and gamma are activated by indomethacin and other non-steroidal anti-inflammatory drugs. J Biol Chem 1997 Feb 7; 272(6): 3406–10PubMedCrossRef

30.

Misra P, Chakrabarti R, Vikramadithyan RK, et al. PAT5A: a partial agonist of peroxisome proliferator-activated receptor gamma is a potent antidiabetic thiazolidinedione yet weakly adipogenic. J Pharmacol Exp Ther 2003 Aug; 306(2): 763–71PubMedCrossRef

31.

Liu K, Black RM, Acton JJ, et al. Selective PPARgamma modulators with improved pharmacological profiles. Bioorg Med Chem Lett 2005 May 16; 15(10): 2437–40PubMedCrossRef

32.

Matsuura H, Adachi H, Smart RC, et al. Correlation between expression of peroxisome proliferator-activated receptor beta and squamous differentiation in epidermal and tracheobronchial epithelial cells. Mol Cell Endocrinol 1999 Jan 25; 147(1–2): 85–92PubMedCrossRef

33.

Rivier M, Safonova I, Lebrun P, et al. Differential expression of peroxisome proliferator-activated receptor subtypes during the differentiation of human keratinocytes. J Invest Dermatol 1998 Dec; 111(6): 1116–21PubMedCrossRef

34.

Westergaard M, Henningsen J, Svendsen ML, et al. Modulation of keratinocyte gene expression and differentiation by PPAR-selective ligands and tetradecylthioacetic acid. J Invest Dermatol 2001 May; 116(5): 702–12PubMedCrossRef

35.

Chen W, Yang CC, Sheu HM, et al. Expression of peroxisome proliferator-activated receptor and CCAAT/enhancer binding protein transcription factors in cultured human sebocytes. J Invest Dermatol 2003 Sep; 121(3): 441–7PubMedCrossRef

36.

Kang HY, Chung E, Lee M, et al. Expression and function of peroxisome proliferator-activated receptors in human melanocytes. Br J Dermatol 2004 Mar; 150(3): 462–8PubMedCrossRef

37.

Billoni N, Buan B, Gautier B, et al. Expression of peroxisome proliferator activated receptors (PPARs) in human hair follicles and PPAR alpha involvement in hair growth. Acta Derm Venereol 2000 Sep; 80(5): 329–34PubMedCrossRef

38.

Ghosh AK, Bhattacharyya S, Lakos G, et al. Disruption of transforming growth factor beta signaling and profibrotic responses in normal skin fibroblasts by peroxisome proliferator-activated receptor gamma. Arthritis Rheum 2004 Apr; 50(4): 1305–18PubMedCrossRef

39.

Westergaard M, Henningsen J, Johansen C, et al. Expression and localization of peroxisome proliferator-activated receptors and nuclear factor kappaB in normal and lesional psoriatic skin. J Invest Dermatol 2003 Nov; 121(5): 1104–17PubMedCrossRef

40.

Nijsten T, Geluyckens E, Colpaert C, et al. Peroxisome proliferator-activated receptors in squamous cell carcinoma and its precursors. J Cutan Pathol 2005 May; 32(5): 340–7PubMedCrossRef

41.

Braissant O, Foufelle F, Scotto C, et al. Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat. Endocrinology 1996 Jan; 137(1): 354–66PubMedCrossRef

42.

Braissant O, Wahli W. Differential expression of peroxisome proliferator-activated receptor-alpha, -beta, and -gamma during rat embryonic development. Endocrinology 1998 Jun; 139(6): 2748–54PubMedCrossRef

43.

Hanley K, Komuves LG, Bass NM, et al. Fetal epidermal differentiation and barrier development In vivo is accelerated by nuclear hormone receptor activators. J Invest Dermatol 1999 Nov; 113(5): 788–95PubMedCrossRef

44.

Michalik L, Desvergne B, Tan NS, et al. Impaired skin wound healing in peroxisome proliferator-activated receptor (PPAR)α and PPARβ mutant mice. J Cell Biol 2001 Aug 20; 154(4): 799–814PubMedCrossRef

45.

Lee SS, Pineau T, Drago J, et al. Targeted disruption of the alpha isoform of the peroxisome proliferator-activated receptor gene in mice results in abolishment of the pleiotropic effects of peroxisome proliferators. Mol Cell Biol 1995 Jun; 15(6): 3012–22PubMed

46.

Barak Y, Nelson MC, Ong ES, et al. PPAR gamma is required for placental, cardiac, and adipose tissue development. Mol Cell 1999 Oct; 4(4): 585–95PubMedCrossRef

47.

Kubota N, Terauchi Y, Miki H, et al. PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance. Mol Cell 1999 Oct; 4(4): 597–609PubMedCrossRef

48.

Peters JM, Lee SS, Li W, et al. Growth, adipose, brain, and skin alterations resulting from targeted disruption of the mouse peroxisome proliferator-activated receptor beta(delta). Mol Cell Biol 2000 Jul; 20(14): 5119–28PubMedCrossRef

49.

Mao-Qiang M, Fowler AJ, Schmuth M, et al. Peroxisome-proliferator-activated receptor (PPAR)-gamma activation stimulates keratinocyte differentiation. J Invest Dermatol 2004 Aug; 123(2): 305–12PubMedCrossRef

50.

Howroyd P, Swanson C, Dunn C, et al. Decreased longevity and enhancement of age-dependent lesions in mice lacking the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha). Toxicol Pathol 2004 Sep; 32(5): 591–9PubMedCrossRef

51.

Schmuth M, Schoonjans K, Yu QC, et al. Role of peroxisome proliferator-activated receptor alpha in epidermal development in utero. J Invest Dermatol 2002 Dec; 119(6): 1298–303PubMedCrossRef

52.

Komuves LG, Hanley K, Jiang Y, et al. Ligands and activators of nuclear hormone receptors regulate epidermal differentiation during fetal rat skin development. J Invest Dermatol 1998 Sep; 111(3): 429–33PubMedCrossRef

53.

Hanley K, Jiang Y, Crumrine D, et al. Activators of the nuclear hormone receptors PPARα and FXR accelerate the development of the fetal epidermal permeability barrier. J Clin Invest 1997 Aug 1; 100(3): 705–12PubMedCrossRef

54.

Hanley K, Jiang Y, He SS, et al. Keratinocyte differentiation is stimulated by activators of the nuclear hormone receptor PPARα. J Invest Dermatol 1998 Apr; 110(4): 368–75PubMedCrossRef

55.

Komuves LG, Hanley K, Lefebvre AM, et al. Stimulation of PPARα promotes epidermal keratinocyte differentiation in vivo. J Invest Dermatol 2000 Sep; 115(3): 353–60PubMedCrossRef

56.

Komuves LG, Hanley K, Man MQ, et al. Keratinocyte differentiation in hyperproliferative epidermis: topical application of PPARα activators restores tissue homeostasis. J Invest Dermatol 2000 Sep; 115(3): 361–7PubMedCrossRef

57.

Muga SJ, Thuillier P, Pavone A, et al. 8S-lipoxygenase products activate peroxisome proliferator-activated receptor alpha and induce differentiation in murine keratinocytes. Cell Growth Differ 2000 Aug; 11(8): 447–54PubMed

58.

Rivier M, Castiel I, Safonova I, et al. Peroxisome proliferator-activated receptor-alpha enhances lipid metabolism in a skin equivalent model. J Invest Dermatol 2000 Apr; 114(4): 681–7PubMedCrossRef

59.

Schmuth M, Haqq CM, Cairns WJ, et al. Peroxisome proliferator-activated receptor (PPAR)-beta/delta stimulates differentiation and lipid accumulation in keratinocytes. J Invest Dermatol 2004 Apr; 122(4): 971–83PubMedCrossRef

60.

Tan NS, Michalik L, Noy N, et al. Critical roles of PPAR beta/ delta in keratinocyte response to inflammation. Genes Dev 2001 Dec 15; 15(24): 3263–77PubMedCrossRef

61.

Di-Poi N, Tan NS, Michalik L, et al. Antiapoptotic role of PPARβ in keratinocytes via transcriptional control of the Akt1 signaling pathway. Mol Cell 2002 Oct; 10(4): 721–33PubMedCrossRef

62.

Kim DJ, Bility MT, Billin AN, et al. PPARbeta/delta selectively induces differentiation and inhibits cell proliferation. Cell Death Differ 2005 Jul 15. Epub ahead of print

63.

Ellis CN, Varani J, Fisher GJ, et al. Troglitazone improves psoriasis and normalizes models of proliferative skin disease: ligands for peroxisome proliferator-activated receptor-gamma inhibit keratinocyte proliferation. Arch Dermatol 2000 May; 136(5): 609–16PubMedCrossRef

64.

Bhagavathula N, Nerusu KC, Lal A, et al. Rosiglitazone inhibits proliferation, motility, and matrix metalloproteinase production in keratinocytes. J Invest Dermatol 2004 Jan; 122(1): 130–9PubMedCrossRef

65.

Venkatraman MS, Chittiboyina A, Meingassner J, et al. Alpha-lipoic acid-based PPARy agonists for treating inflammatory skin diseases. Arch Dermatol Res 2004 Aug; 296(3): 97–104PubMedCrossRef

66.

Nickoloff BJ, Qin JZ, Chaturvedi V, et al. Jagged-1 mediated activation of notch signaling induces complete maturation of human keratinocytes through NF-κB and PPARγ. Cell Death Differ 2002 Aug; 9(8): 842–55PubMedCrossRef

67.

Ghoreschi K, Rocken M. Immune deviation strategies in the therapy of psoriasis. Curr Drug Targets Inflamm Allergy 2004 Jun; 3(2): 193–8PubMedCrossRef

68.

Clark RB, Bishop-Bailey D, Estrada-Hernandez T, et al. The nuclear receptor PPAR gamma and immunoregulation: PPAR gamma mediates inhibition of helper T cell responses. J Immunol 2000 Feb 1; 164(3): 1364–71PubMed

69.

Gosset P, Charbonnier AS, Delerive P, et al. Peroxisome proliferator-activated receptor gamma activators affect the maturation of human monocyte-derived dendritic cells. Eur J Immunol 2001 Oct; 31(10): 2857–65PubMedCrossRef

70.

Rosenfield RL, Deplewski D, Kentsis A, et al. Mechanisms of androgen induction of sebocyte differentiation. Dermatology 1998; 196(1): 43–6PubMedCrossRef

71.

Rosenfield RL, Kentsis A, Deplewski D, et al. Rat preputial sebocyte differentiation involves peroxisome proliferator-activated receptors. J Invest Dermatol 1999 Feb; 112(2): 226–32PubMedCrossRef

72.

Kim MJ, Ciletti N, Michel S, et al. The role of specific retinoid receptors in sebocyte growth and differentiation in culture. J Invest Dermatol 2000 Feb; 114(2): 349–53PubMedCrossRef

73.

Kim MJ, Deplewski D, Ciletti N, et al. Limited cooperation between peroxisome proliferator-activated receptors and retinoid X receptor agonists in sebocyte growth and development. Mol Genet Metab 2001 Nov; 74(3): 362–9PubMedCrossRef

74.

Wrobel A, Scitmann H, Fimmel S, et al. Differentiation and apoptosis in human immortalized sebocytes. J Invest Dermatol 2003 Feb; 120(2): 175–81PubMedCrossRef

75.

Zouboulis C, Chen W, Alestas T, et al. Sexual hormones utilize complex mechanisms to modulate sebocyte differentiation. Exp Dermatol 2005 Feb; 14(2): 156CrossRef

76.

Zouboulis C, Saborowski A, Boschnakow A. Zileuton, an oral 5-lipoxygenase inhibitor, directly reduces sebum production. Dermatology 2005; 210(1): 36–8PubMedCrossRef

77.

Downie MM, Sanders DA, Maier LM, et al. Peroxisome proliferator-activated receptor and farnesoid X receptor ligands differentially regulate sebaceous differentiation in human sebaceous gland organ cultures in vitro. Br J Dermatol 2004 Oct; 151(4): 766–75PubMedCrossRef

78.

Daynes RA, Jones DC. Emerging roles of PPARs in inflammation and immunity. Nat Rev Immunol 2002 Oct; 2(10): 748–59PubMedCrossRef

79.

Kippenberger S, Loitsch SM, Grundmann-Kollmann M, et al. Activators of peroxisome proliferator-activated receptors protect human skin from ultraviolet-B-light-induced inflammation. J Invest Dermatol 2001 Dec; 117(6): 1430–6PubMedCrossRef

80.

Zhang Q, Southall MD, Mezsick SM, et al. Epidermal peroxisome proliferator-activated receptor gamma as a target for ultraviolet B radiation. J Biol Chem 2005 Jan 7; 280(1): 73–9PubMed

81.

Sheu MY, Fowler AJ, Kao J, et al. Topical peroxisome proliferator activated receptor-alpha activators reduce inflammation in irritant and allergic contact dermatitis models. J Invest Dermatol 2002 Jan; 118(1): 94–101PubMedCrossRef

82.

Lo VJ, Fu J, Astarita G, et al. The nuclear receptor peroxisome proliferator-activated receptor-alpha mediates the anti-inflammatory actions of palmitoylethanolamide. Mol Pharmacol 2005 Jan; 67(1): 15–9CrossRef

83.

Ruhl R, Dahten A, Schweigert FJ, et al. Inhibition of IgE-production by peroxisome proliferator-activated receptor ligands. J Invest Dermatol 2003 Oct; 121(4): 757–64PubMedCrossRef

84.

Fowler AJ, Sheu MY, Schmuth M, et al. Liver X receptor activators display anti-inflammatory activity in irritant and allergic contact dermatitis models: liver-X-receptor-specific inhibition of inflammation and primary cytokine production. J Invest Dermatol 2003 Feb; 120(2): 246–55PubMedCrossRef

85.

Komuves LG, Schmuth M, Fowler AJ, et al. Oxysterol stimulation of epidermal differentiation is mediated by liver X receptor-beta in murine epidermis. J Invest Dermatol 2002 Jan; 118(1): 25–34PubMedCrossRef

86.

Hanley K, Ng DC, He SS, et al. Oxysterols induce differentiation in human keratinocytes and increase Ap-1-dependent in-volucrin transcription. J Invest Dermatol 2000 Mar; 114(3): 545–53PubMedCrossRef

87.

Michalik L, Desvergne B, Wahli W. Peroxisome-proliferator-activated receptors and cancers: complex stories. Nat Rev Cancer 2004 Jan; 4(1): 61–70PubMedCrossRef

88.

Thuillier P, Anchiraico GJ, Nickel KP, et al. Activators of peroxisome proliferator-activated receptor-alpha partially inhibit mouse skin tumor promotion. Mol Carcinog 2000 Nov; 29(3): 134–42PubMedCrossRef

89.

Kim DJ, Akiyama TE, Harman FS, et al. Peroxisome proliferator-activated receptor beta (delta)-dependent regulation of ubiquitin C expression contributes to attenuation of skin carci-nogenesis. J Biol Chem 2004 May 28; 279(22): 23719–27PubMedCrossRef

90.

Kim DJ, Murray IA, Burns AM, et al. Peroxisome proliferator-activated receptor-beta/delta inhibits epidermal cell proliferation by down-regulation of kinase activity. J Biol Chem 2005 Mar 11; 280(10): 9519–27PubMedCrossRef

91.

Pineau T, Hudgins WR, Liu L, et al. Activation of a human peroxisome proliferator-activated receptor by the antitumor agent phenylacetate and its analogs. Biochem Pharmacol 1996 Aug 23; 52(4): 659–67PubMedCrossRef

92.

Mossner R, Schulz U, Kruger U, et al. Agonists of peroxisome proliferator-activated receptor gamma inhibit cell growth in malignant melanoma. J Invest Dermatol 2002 Sep; 119(3): 576–82PubMedCrossRef

93.

Seargent JM, Yates EA, Gill JH. GW9662, a potent antagonist of PPARy, inhibits growth of breast tumour cells and promotes the anticancer effects of the PPARγ agonist rosiglitazone, independently of PPARy activation. Br J Pharmacol 2004 Dec; 143(8): 933–7PubMedCrossRef

94.

He G, Thuillier P, Fischer SM. Troglitazone inhibits cyclin D1 expression and cell cycling independently of PPARγ in normal mouse skin keratinocytes. J Invest Dermatol 2004 Dec; 123(6): 1110–9PubMedCrossRef

95.

He G, Muga S, Thuillier P, et al. The effect of PPARgamma ligands on UV- or chemically-induced carcinogenesis in mouse skin. Mol Carcinog 2005 Aug; 43(4): 198–206PubMedCrossRef

96.

Nicol CJ, Yoon M, Ward JM, et al. PPARγ influences susceptibility to DMBA-induced mammary, ovarian and skin carcinogenesis. Carcinogenesis 2004 Sep; 25(9): 1747–55PubMedCrossRef

97.

Kang WH, Chun SC, Lee S. Intermittent therapy for melasma in Asian patients with combined topical agents (retinoic acid, hydroquinone and hydrocortisone): clinical and histological studies. J Dermatol 1998 Sep; 25(9): 587–96PubMed

98.

Ando H, Ryu A, Hashimoto A, et al. Linoleic acid and alpha-linolenic acid lightens ultraviolet-induced hyperpigmentation of the skin. Arch Dermatol Res 1998 Jul; 290(7): 375–81PubMedCrossRef

99.

Shigeta Y, Imanaka H, Ando H, et al. Skin whitening effect of linoleic acid is enhanced by liposomal formulations. Biol Pharm Bull 2004 Apr; 27(4): 591–4PubMedCrossRef

100.

Parsad D, Saini R, Verma N. Combination of PUVAsol and topical calcipotriol in vitiligo. Dermatology 1998; 197(2): 167–70PubMedCrossRef

101.

Ameen M, Exarchou V, Chu AC. Topical calcipotriol as monotherapy and in combination with psoralen plus ultraviolet A in the treatment of vitiligo. Br J Dermatol 2001 Sep; 145(3): 476–9PubMedCrossRef

102.

Ando H, Watabe H, Valencia JC, et al. Fatty acids regulate pigmentation via proteasomal degradation of tyrosinase: a new aspect of ubiquitin-proteasome function. J Biol Chem 2004 Apr 9; 279(15): 15427–33PubMedCrossRef

103.

Di-Poi N, Michalik L, Tan NS, et al. The anti-apoptotic role of PPARβ contributes to efficient skin wound healing. J Steroid Biochem Mol Biol 2003 Jun; 85(2–5): 257–65PubMedCrossRef

104.

Tan NS, Michalik L, Di-Poi N, et al. Essential role of Smad3 in the inhibition of inflammation-induced PPARbeta/delta expression. EMBO J 2004 Oct 27; 23(21): 4211–21PubMedCrossRef

105.

Michalik L, Feige JN, Gelman L, et al. Selective expression of a dominant negative form of PPAR in keratinocytes leads to impaired epidermal healing. Mol Endocrinol 2005 May 12. Epub ahead of print

106.

Tan NS, Michalik L, Desvergne B, et al. Genetic- or transforming growth factor-betal-induced changes in epidermal peroxisome proliferator-activated receptor beta/delta expression dictate wound repair kinetics. J Biol Chem 2005 May 6; 280(18): 18163–70PubMedCrossRef

107.

Di-Poi N, Ng CY, Tan NS, et al. Epithelium-mesenchyme interactions control the activity of peroxisome proliferator-activated receptor beta/delta during hair follicle development. Mol Cell Biol 2005 Mar; 25(5): 1696–712PubMedCrossRef

108.

Peng XD, Xu PZ, Chen ML, et al. Dwarfism, impaired skin development, skeletal muscle atrophy, delayed bone development, and impeded adipogenesis in mice lacking Aktl and Akt 2. Genes Dev 2003 Jun 1; 17(11): 1352–65PubMedCrossRef

109.

Imamura T, Takata I, Ogasawara M, et al. Clofibrate treatment of psoriasis with hypertriglycemia: clinical, histological and laboratory analysis [in Japanese]. Nippon Hifuka Gakkai Zasshi 1991 May; 101(6): 623–8PubMed

110.

Pershadsingh HA, Sproul JA, Benjamin E, et al. Treatment of psoriasis with troglitazone therapy. Arch Dermatol 1998 Oct; 134(10): 1304–5PubMedCrossRef

111.

Shafiq N, Malhotra S, Pandhi P, et al. Pilot trial: Pioglitazone versus placebo in patients with plaque psoriasis (the P6). Int J Dermatol 2005 Apr; 44(4): 328–33PubMedCrossRef

112.

Bongartz T, Coras B, Vogt T, et al. Treatment of active psoriatic arthritis with the PPARgamma ligand pioglitazone: an open-label pilot study. Rheumatology (Oxford) 2005 Jan; 44(1): 126–9CrossRef

113.

Kuenzli S, Saurat JH. Effect of topical PPARbeta/delta and PPARgamma agonists on plaque psoriasis: a pilot study. Dermatology 2003; 206(3): 252–6PubMedCrossRef

114.

Mossner R, Kaiser R, Matern P, et al. Variations in the genes encoding the peroxisome proliferator-activated receptors alpha and gamma in psoriasis. Arch Dermatol Res 2004 Jun; 296(1): 1–5PubMedCrossRef

115.

Chawla A, Barak Y, Nagy L, et al. PPAR-gamma dependent and independent effects on macrophage-gene expression in lipid metabolism and inflammation. Nat Med 2001 Jan; 7(1): 48–52PubMedCrossRef

116.

Cunard R, DiCampli D, Archer DC, et al. WY14,643, a PPAR alpha ligand, has profound effects on immune responses in vivo. J Immunol 2002 Dec 15; 169(12): 6806–12PubMed

117.

Hutley LJ, Newell FM, Joyner JM, et al. Effects of rosiglitazone and linoleic acid on human preadipocyte differentiation. Eur J Clin Invest 2003 Jul; 33(7): 574–81PubMedCrossRef

118.

Ouamrane L, Larrieu G, Gauthier B, et al. RXR activators molecular signalling: involvement of a PPAR alpha-dependent pathway in the liver and kidney, evidence for an alternative pathway in the heart. Br J Pharmacol 2003 Mar; 138(5): 845–54PubMedCrossRef

119.

IJpenberg A, Tan NS, Gelman L, et al. In vivo activation of PPAR target genes by RXR homodimers. EMBO J 2004 May 19; 23(10): 2083–91PubMedCrossRef

120.

Kersten S, Seydoux J, Peters JM, et al. Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting. J Clin Invest 1999 Jun; 103(11): 1489–98PubMedCrossRef

121.

Shaw N, Elholm M, Noy N. Retinoic acid is a high affinity selective ligand for the peroxisome proliferator-activated receptor beta/delta. J Biol Chem 2003 Oct 24; 278(43): 41589–92PubMedCrossRef

Titel: Peroxisome Proliferator-Activated Receptors and their Ligands
Entry Into the Post-Glucocorticoid Era of Skin Treatment?
verfasst von: Günther Weindl
Monika Schäfer-Korting
Martin Schaller
Hans Christian Korting
Publikationsdatum: 01.10.2005
Verlag: Springer International Publishing
Erschienen in: Drugs / Ausgabe 14/2005
Print ISSN: 0012-6667
Elektronische ISSN: 1179-1950
DOI: https://doi.org/10.2165/00003495-200565140-00002

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Abstract

Die Highlights vom Kongress des American College of Cardiology 2024

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Abstract

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