Skip to main content

Advertisement

SpringerLink
Log in

Peroxisome proliferator-activated receptors (PPARs) and PPAR agonists: the ‘future’ in dermatology therapeutics?

  • Review
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

Abstract

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors and comprise three different isoforms namely PPARα, PPARγ, and PPARβ/δ with PPARβ/δ being the predominant subtype in human keratinocytes. After binding with specific ligands, PPARs regulate gene expression, cell growth and differentiation, apoptosis, inflammatory responses, and tumorogenesis. PPARs also modulate a wide variety of skin functions including keratinocyte proliferation, epidermal barrier formation, wound healing, melanocyte proliferation, and sebum production. Recent studies have shown the importance of PPARs in the pathogenesis of many dermatological disorders. Clinical trials have suggested possible role of PPAR agonists in the management of various dermatoses ranging from acne vulgaris, psoriasis, hirsutism, and lipodystrophy to cutaneous malignancies including melanoma. This article is intended to be a primer for dermatologists in their understanding of clinical relevance of PPARs and PPAR agonists in dermatology therapeutics.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Abraham DJ, Eckes B, Rajkumar V, Krieg T (2007) New developments in fibroblast and myofibroblast biology: implications for fibrosis and scleroderma. Curr Rheumatol Rep 9:136–143

    Article  CAS  PubMed  Google Scholar 

  2. Amr K, Abdel-Hameed M, Sayed K, Nour-Edin F, Abdel Hay R (2014) The Pro12Ala polymorphism of the gene for peroxisome proliferator-activated receptor gamma is associated with a lower Global Acne Grading System score in patiemts with acne vulgaris. Clin Exp Dermatol 39:741–745

    Article  CAS  PubMed  Google Scholar 

  3. Arioglu E, Duncan-Morin J, Sebring N, Rother KI, Gottlieb N, Lieberman J et al (2000) Efficacy and safety of troglitazone in the treatment of lipodystrophy syndromes. Ann Intern Med 133:263–274

    Article  CAS  PubMed  Google Scholar 

  4. Behshad R, Cooper KD, Korman NJ (2008) A retrospective case series review of the peroxisome proliferator-activated receptor ligand rosiglitazone in the treatment of atopic dermatitis. Arch Dermatol 144:84–88

    Article  CAS  PubMed  Google Scholar 

  5. Bongartz T, Coras B, Vogt T, Scholmerich J, Muller-Ladner U (2005) Treatment of active psoriatic arthritis with the PPARγ ligand pioglitazone: an open-label pilot study. Rheumatology 44:126–129

    Article  CAS  PubMed  Google Scholar 

  6. Botton T, Puissant A, Bahadoran P, Annicotte JS, Fajas L, Ortonne JP et al (2009) In vitro and in vivo anti-melanoma effects of ciglitazone. J Invest Dermatol 129:1208–1212

    Article  CAS  PubMed  Google Scholar 

  7. Braissant O, Wahli W (1998) Differential expression of peroxisome proliferator-activated receptor-alpha-beta, and -gamma during rat embryonic development. Endocrinology 139:2748–2754

    CAS  PubMed  Google Scholar 

  8. Burgess HA, Daugherty LE, Thatcher TH, Lakatos HF, Ray DM, Redonnnet M et al (2005) PPAR gamma agonists inhibit TGF-beta induced pulmonary myofibroblasts differentiation and collagen production: implications for therapy of lung fibrosis. Am J Physiol Lung Cell Mol Physiol 288:L1146–L1153

    Article  CAS  PubMed  Google Scholar 

  9. Caron M, Vigouroux C, Bastard J-P, Capeau J (2009) Antiretroviral-related adipocyte dysfunction and lipodystrophy in HIV-infected patients: alteration of the PPARγ-dependent pathways. PPAR Res 2009:507141. doi:10.1155/2009/507141

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  10. Carr A, Workman C, Carey D, Rogers G, Martin A, Baker D et al (2004) No effect of Rosiglitazone for treatment of HIV-1 lipoatrophy: randomised, double-blind, placebo-controlled trial. Lancet 363:429–438

    Article  CAS  PubMed  Google Scholar 

  11. Cavalcanti RB, Raboud J, Shen S, Kain KC, Cheung A, Walmsley S (2007) A randomized, placebo-controlled trial of rosiglitazone for HIV-related lipoatrophy. J Infect Dis 195:1754–1761

    Article  CAS  PubMed  Google Scholar 

  12. Chen W, Yang CC, Sheu HM, Seltmann H, Zouboulis CC (2003) Expression of peroxisome proliferator-activated receptor and CCAAT/enhancer binding protein transcription factors in cultured human sebocytes. J Invest Dermatol 121:441–447

    Article  CAS  PubMed  Google Scholar 

  13. Chiba T, Takeuchi S, Esaki H, Yamamura K, Kurihara K, Moroi Y et al (2012) Topical application of PPAR alpha (but not beta/delta or gamma) suppresses atopic dermatitis in NC/Nga mice. Allergy 67:936–942

    Article  CAS  PubMed  Google Scholar 

  14. Clark RB (2002) The role of PPARs in inflammation and immunity. J Leukoc Bio 71:388–400

    CAS  Google Scholar 

  15. Coras B, Hafner C, Reichle A, Hohenleutner U, Szeimies RM, Landthaler M et al (2004) Antiangiogenic therapy with pioglitazone, rofecoxib, and trofosfamide in a patient with endemic Kaposi sarcoma. Arch Dermatol 140:1504–1507

    Article  PubMed  Google Scholar 

  16. Critical therapeutics announces results from phase II study of Zileuton in acne patients. http://www.businesswire.com/news/home/20050714005349/en/Critical-Therapeutics-Announces-Results-Phase-II-Study#.VLZ9DiuUdR4. Accessed 20 Nov 2014

  17. Dahten MS, Worm M (2007) PPAR gamma expression profile and its cytokine driven regulation in atopic dermatitis. Allergy 62:926–933

    Article  CAS  PubMed  Google Scholar 

  18. Demerjian M, Choi EH, Man S, Chang S, Elias PM, Feingold KR (2009) Activators of PPARs and LXR decrease the adverse effects of exogenous glucocorticoids on the epidermis. Exp Dermatol 18:643–649

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Dereli D, Dereli T, Bayraktar F, Ozgen AG, Yilmaz C (2005) Endocrine and metabolic effects of rosiglitazone in non-obese women with polycystic ovary disease. Endocr J 52:299–308

    Article  CAS  PubMed  Google Scholar 

  20. Di-Poi N, Michalik L, Desvergne B, Wahli W (2004) Functions of peroxisome proliferator-activated receptors (PPAR) in skin homeostasis. Lipids 39:1093–1099

    Article  CAS  PubMed  Google Scholar 

  21. Di-Poi N, Ng CY, Tan NS, Yang Z, Hemmings BA, Desvergne B et al (2005) Epithelium-mesenchyme interactions control the activity of peroxisome proliferator-activated receptor β/δ during hair follicle development. Mol Cell Biol 25:1696–1712

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Eichenfield LF, McCollum A, Msika P (2009) The benefits of sunflower oleodistillate (SOD) in pediatric dermatology. Pediatr Dermatol 26:669–675

    Article  PubMed  Google Scholar 

  23. Elbrecht A, Chen Y, Cullinan CA, Hayes N, Leibowitz M, Moller DE et al (1996) Molecular cloning, expression and characterization of human peroxisome proliferator activated receptors gamma 1 and gamma 2. Biochem Biophys Res Commun 224:431–437

    Article  CAS  PubMed  Google Scholar 

  24. Ellis CN, Varani J, Fisher GJ, Zeigler ME, Pershadsingh HA, Benson SC et al (2000) Troglitazone improves psoriasis and normalizes models of proliferative skin disease: ligands for peroxisome proliferator-activated receptor-gamma inhibit keratinocyte proliferation. Arch Dermatol 136:609–616

    Article  CAS  PubMed  Google Scholar 

  25. Elmongy NN, Shaker O (2012) Expression of peroxisome proliferator activator receptor β/δ in acne vulgaris. Eur J Dermatol 22:42–45

    CAS  PubMed  Google Scholar 

  26. Freudlsperger C, Moll I, Schumacher U, Thies A (2006) Anti-proliferative effect of peroxisome proliferator-activated receptor gamma agonists on human malignant melanoma cells in vitro. Anticancer Drugs 17:325–332

    Article  CAS  PubMed  Google Scholar 

  27. Friedmann PS, Cooper HL, Healy E (2005) Peroxisome proliferator-activated receptors and their relevance to dermatology. Acta Derm Venereol 85:194–202

    Article  CAS  PubMed  Google Scholar 

  28. Gosset P, Charbonnier AS, Delerive P, Fontaine J, Staels B, Pestel J et al (2001) Peroxisome proliferator activated receptor gamma activators affect the maturation of human monocyte derived dendritic cells. Eur J Immunol 21:2857–2862

    Article  Google Scholar 

  29. Grabacka M, Placha W, Plonka PM, Pajak S, Urbanska K, Laidler P, Slominski A (2004) Inhibition of melanoma metastases by fenofibrate. Arch Dermatol Res 296:54–58

    Article  CAS  PubMed  Google Scholar 

  30. Hack K, Reilly L, Palmer C, Read KD, Norval S, Kime R et al (2012) Skin targeted inhibition of PPAR β/δ by selective antagonists to treat PPAR β/δ mediated psoriasis-like skin disease. PLoS One 7:e37097

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Hadigan C, Yawetz S, Thomas A, Havers F, Sax PE, Grinspoon S (2004) Metabolic effects of rosiglitazone in HIV lipodystrophy: a randomized controlled trial. Ann Intern Med 140:786–794

    Article  CAS  PubMed  Google Scholar 

  32. Hanley K, Kömüves LG, Bass NM, He SS, Jiang Y, Crumrine D et al (1999) Fetal epidermal differentiation and barrier development in vivo is accelerated by nuclear hormone receptor activators. J Invest Dermatol 113:788–795

    Article  CAS  PubMed  Google Scholar 

  33. Harris SG, Phipps RP (2001) The nuclear receptor PPAR gamma is expressed by mouse T lymphocytes and PPAR gamma agonists induce apoptosis. Eur J Immunol 31:1098–1105

    Article  CAS  PubMed  Google Scholar 

  34. Hatano Y, Man MQ, Uchida Y, Crumrine D, Mauro TM, Elias PM et al (2010) Murine atopic dermatitis responds to peroxisome proliferator activated receptor α, β/δ (but not γ), and liver-X-receptor activators. J Allergy Clin Immunol 125:160–169

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Icre G, Wahli W, Michalik L (2006) Functions of the peroxisome proliferator-activated receptor (PPAR) α and β in skin homeostasis, epithelial repair, and morphogenesis. J Investig Dermatol Symp Proc 11:30–35

    Article  CAS  PubMed  Google Scholar 

  36. Issemann I, Green S (1990) Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 347:645–650

    Article  CAS  PubMed  Google Scholar 

  37. Javiya VA, Patel JA (2006) The role of peroxisome-proliferator activated receptors in human disease. Indian J Pharmacol 38:243–253. doi:10.4103/0253-7613.27020

    Article  CAS  Google Scholar 

  38. Kanakasabai S, Cherwae W, Walline CC, Iams W, Adams SM, Bright JJ (2010) Peroxisome proliferator-activated receptor δ agonists inhibit T helper type 1 (Th1) and Th17 responses in experimental allergic encephalomyelitis. Immunology 130:572–588

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Kang HY, Chung E, Lee M, Cho Y, Kang WH (2004) Expression and function of peroxisome proliferator-activated receptors in human melanocytes. Br J Dermatol 150:462–468

    Article  CAS  PubMed  Google Scholar 

  40. Kapoor M, McCann M, Liu S, Huh K, Denton CP, Abraham DJ et al (2009) Loss of PPARγ in mouse fibroblasts results in increased susceptibility to bleomycin-induced skin fibrosis. Arthritis Rheum 60:2822–2829

    Article  CAS  PubMed  Google Scholar 

  41. Karnik P, Tekeste Z, McCormick TS, Gilliam AC, Price VH, Cooper KD et al (2009) Hair follicle stem cell-specific PPAR-gamma deletion causes scarring alopecia. J Invest Dermatol 129:1243–1257

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Klotz L, Burgdorf S, Dani I, Saijo K, Flossdorf J, Hucke S et al (2009) The nuclear receptor PPAR gamma selectively inhibits Th17 differentiation in a T cell-intrinsic fashion and suppresses CNS autoimmunity. J Exp Med 206:2079–2089

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  43. Kömüves LG, Hanley K, Jiang Y, Elias PM, Willium ML, Feingold KR (1998) Ligands and activators of nuclear hormone receptors regulate epidermal differentiation during fetal rat skin development. J Invest Dermatol 111:429–433

    Article  PubMed  Google Scholar 

  44. Kömüves LG, Hanley K, Man MQ, Elias PM, Williams ML, Feingold KR (2000) Keratinocyte differentiation in hyperproliferative epidermis: topical application of PPAR alpha activators restores tissue homeostasis. J Invest Dermatol 115:361–367

    Article  PubMed  Google Scholar 

  45. Kuenzli S, Saurat JH (2003) Peroxisome proliferator-activated receptors in cutaneous biology. Br J Dermatol 149:229–236

    Article  CAS  PubMed  Google Scholar 

  46. Kuenzli S, Saurat JH (2003) Effect of topical PPARβ/δ and PPARγ agonists on plaque psoriasis. A pilot study. Dermatology 206:252–256

    Article  CAS  PubMed  Google Scholar 

  47. Lajevardi V, Hallaji Z, Daklan S, Abedini R, Goodarzi A, Abdolreza M (2015) The efficacy of methotrexate plus pioglitazone vs. methotrexate alone in the management of patients with plaque-type psoriasis: a single-blinded randomized controlled trial. Int J Dermatol 54:95–101

    Article  CAS  PubMed  Google Scholar 

  48. Liu Y, Meng Y, Li H, Li J, Fu J, Liu Y et al (2006) Growth inhibition and differentiation induced by peroxisome proliferator activated receptor gamma ligand rosiglitazone in human melanoma cell line A375. Med Oncol 23:393–402

    Article  PubMed  Google Scholar 

  49. Ludtke A, Heck K, Genschel J, Mehnert H, Spuler S, Worman HJ et al (2005) Long-term treatment experience in a subject with Dunnigan-type familial partial lipodystrophy: efficacy of rosiglitazone. Diabet Med 22:1611–1613

    Article  CAS  PubMed  Google Scholar 

  50. Man MQ, Barish GD, Schmuth D, Crumrine Y, Barak S, Chang Y et al (2008) Deficiency of PPAR beta/delta in the epidermis results in defective cutaneous permeability barrier homeostasis and increased inflammation. J Invest Dermatol 128:370–377

    Article  CAS  PubMed  Google Scholar 

  51. Mahgoub D, El Tawdy AM, Metwally D, Manar A, Rashed L (2014) Estmation of peroxisome-proliferator-activated receptor γ gene expression in inflammatory skin diseases: atopic dermatitis and psoriasis. Our Dermatol Online 5:107–112

    Article  Google Scholar 

  52. Mao-Qiang M, Fowler AJ, Schmuth M, Lau P, Chang S, Brown BE et al (2004) Peroxisome-proliferator-activated receptor (PPAR)-gamma activation stimulates keratinocyte differentiation. J Invest Dermatol 123:305–312

    Article  CAS  PubMed  Google Scholar 

  53. Marx N, Kehrle B, Kohlhammer K, Grub M, Koenig W, Hombach V et al (2002) PPAR activators as anti-inflammatory mediators in human T lymphocytes; implications for atherosclerosis and transplantation-associated arteriosclerosis. Circ Res 90:703–710

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. Masuda T, Wada K, Nakajima A, Okura M, Kudo C, Kadowaki T et al (2005) Critical role of peroxisome proliferator-activated receptor gamma on anoikis and invasion of squamous cell carcinoma. Clin Cancer Res 11:4012–4021

    Article  CAS  PubMed  Google Scholar 

  55. Michalik L, Desvergne B, Tan NS, Basu-Modak S, Escher P, Rieusset J et al (2001) Impaired skin wound healing in peroxisome proliferator-activated receptor (PPAR) alpha and PPAR beta mutant mice. J Cell Biol 154:799–814

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  56. Michiels JF, Perrin C, Leccia N, Massi D, Grimaldi P, Wagner N (2010) PPARβ activation inhibits melanoma cell proliferation involving repression of the Wilms’ tumour suppressor WT1. Pflugers Arch 459:689–703

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  57. Mirmirani P, Karnik P (2009) Lichen planopilaris treated with a peroxisome proliferator-activated receptor gamma agonist. Arch Dermatol 145:1363–1366

    Article  PubMed Central  PubMed  Google Scholar 

  58. Montagner A, Wahli W (2013) Contributions of peroxisome proliferator-activated receptor β/δ to skin health and disease. Biomol Concepts 4:53–64

    Article  CAS  PubMed  Google Scholar 

  59. Mossner R, Schulz U, Kruger U, Middel P, Schinner S, Fuzesi L et al (2002) Agonists of peroxisome proliferator-activated receptor γ inhibit cell growth in malignant melanoma. J Invest Dermatol 119:576–582

    Article  CAS  PubMed  Google Scholar 

  60. Mulligan K, Yang Y, Wininger DA, Koletar SL, Parker RA, Alston-Smith BL et al (2007) Effects of metformin and rosiglitazone in HIV-infected patients with hyperinsulinemia and elevated waist/hip ratio. AIDS 21:47–57

    Article  CAS  PubMed  Google Scholar 

  61. Neher MD, Weckbach S, Huber-Lang MS, Stahel PF (2012) New insights into the role of peroxisome proliferator-activated receptors in regulating the inflammatory response after tissue injury. PPAR Res. doi:10.1155/2012/728461

    PubMed Central  PubMed  Google Scholar 

  62. Nencioni A, Grunebach F, Zobywlaski A, Denzlinger C, Brugger W, Brossart P (2002) Dendritic cell immunogenicity is regulated by peroxisome proliferator-activated receptor gamma. J Immunol 169:1228–1235

    Article  CAS  PubMed  Google Scholar 

  63. Nicol CJ, Yoon M, Ward JM, Yamashita M, Fukamachi K, Peters JM et al (2004) PPAR{gamma} influences susceptibility to DMBA-induced mammary, ovarian and skin carcinogenesis. Carcinogenesis 25:1747–1755

    Article  CAS  PubMed  Google Scholar 

  64. Nijsten T, Colpaert CG, Vermeulen PB, Harris AL, Van Marck E, Lambert J (2004) Cyclooxygenase-2 expression and angiogenesis in squamous cell carcinoma of the skin and its precursors: a paired immunohistochemical study of 35 cases. Br J Dermatol 151:837–845

    Article  CAS  PubMed  Google Scholar 

  65. Nijsten T, Geluyckens E, Colpaert C, Lambert J (2005) Peroxisome proliferator-activated receptors in squamous cell carcinoma and its precursors. J Cutan Pathol 32:340–347

    Article  PubMed  Google Scholar 

  66. Owen KR, Donohoe M, Ellard S, Hattersley AT (2003) Response to treatment with rosiglitazone in familial partial lipodystrophy due to a mutation in the LMNA gene. Diabetic Med 20:823–827

    Article  PubMed  Google Scholar 

  67. Panigrahy D, Shen LQ, Kieran MW, Kaipainen A (2003) Therapeutic potential of thiazolidinediones as anticancer agents. Expert Opin Investig Drugs 12:1925–1937

    Article  CAS  PubMed  Google Scholar 

  68. Panigrahy D, Singer S, Shen LQ, Butterfield CE, Freedman DA, Chen EJ et al (2002) PPAR gamma ligands inhibit primary tumor growth and metastasis by inhibiting angiogenesis. J Clin Invest 110:923–932

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  69. Pasceri V, Wu HD, Willerson JT, Yeh ET (2000) Modulation of vascular inflammation in vitro and in vivo by peroxisome proliferator-activated receptor-gamma activators. Circulation 101:235–238

    Article  CAS  PubMed  Google Scholar 

  70. Pershadsingh HA, Sproul JA, Benjamin E, Finnegan J, Amin NM (1998) Treatment of psoriasis with troglitazone therapy. Arch Dermatol 134:1304–1305

    Article  CAS  PubMed  Google Scholar 

  71. Placha W, Gil D, Dembinska-Kiec A, Laidler P (2003) The effect of PPAR gamma ligands on the proliferation and apoptosis of human melanoma cells. Melanoma Res 13:447–456

    Article  CAS  PubMed  Google Scholar 

  72. Plager DA, Leontovich AA, Henke SA, Davis MD, McEvoy MT, Sciallis GF 2nd et al (2007) Early cutaneous gene transcription changes in adult atopic dermatitis and potential clinical implications. Exp Dermatol 16:28–36

    Article  CAS  PubMed  Google Scholar 

  73. Raboud JM, Dlong C, Carr A, Grinspoon S, Mulligan K, Sutinen J et al (2010) A meta-analysis of six placebo-controlled trials of thiazolidinedione therapy for HIV lipoatrophy. HIV Clin Trials 11:39–50

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  74. Ricote M, Glass CK (2007) PPARs and molecular mechanisms of transrepression. Biochim Biophys Acta 1771:926–935

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  75. Romanowska M, Reilly L, Palmer CN, Gustafsson MC, Foerster J (2010) Activation of PPAR β/δ causes a psoriasis-like skin disease in vivo. PLoS One 5:e9701

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  76. Rosenfield RL, Deplewski D, Kentsis A, Ciletti N (1998) Mechanisms of androgen induction of sebocyte differentiation. Dermatology 196:43–46

    Article  CAS  PubMed  Google Scholar 

  77. Rosenfield RL, Kentsis A, Deplewski D, Ciletti N (1999) Rat preputial sebocyte differentiation involves peroxisome proliferator-activated receptors. J Invest Dermatol 112:226–232

    Article  CAS  PubMed  Google Scholar 

  78. Rühl R, Dahten A, Schweigert FJ, Herz U, Worm M (2003) Inhibition of IgE-production by peroxisome proliferator-activated receptor ligands. J Invet Dermatol 121:757–764

    Article  Google Scholar 

  79. Shafiq N, Malhotra S, Pandhi P, Gupta M, Kumar B, Sandhu K (2005) Pilot trial: pioglitazone versus placebo in patients with plaque psoriasis (the P6). Int J Dermatol 44:328–333

    Article  CAS  PubMed  Google Scholar 

  80. Schamitt JI, Zhang Z, Wozel G, Meurer M, Kirch W (2008) Efficacy and tolerability of biologic and non-biologic systemic treatments for moderate-to-severe psoriasis: meta-analysis of randomized controlled trials. Br J Dermatol 159:513–526

    Article  CAS  Google Scholar 

  81. Schmuth M, Haqq CM, Cairns WJ, Holder JC, Dorsam S, Chang S et al (2004) Peroxisome proliferator-activated receptor (PPAR)-β/δ Stimulates differentiation and lipid accumulation in keratinocytes. J Invest Dermatol 122:971–983

    Article  CAS  PubMed  Google Scholar 

  82. Schmuth M, Moosbrugger-Martinz V, Blunder S, Dubrac S (2014) Role of PPAR, LXR, and PXR in epidermal homeostasis and inflammation. Biochim Biophys Acta 1841:463–473

    Article  CAS  PubMed  Google Scholar 

  83. Schmuth M, Schoonjans K, Yu QC, Fluhr JW, Crumrine D, Hachem JP et al (2002) Role of peroxisome proliferator-activated receptor alpha in epidermal development in utero. J Invest Dermatol 119:1298–1303

    Article  CAS  PubMed  Google Scholar 

  84. Schuster M, Zouboulis CC, Ochsendorf F, Muller J, Thaci D, Bernd A et al (2011) Peroxisome proliferator-activated receptor activators protect sebocytes from apoptosis: a new treatment modality for acne? Br J Dermatol 164:182–186

    Article  CAS  PubMed  Google Scholar 

  85. Sertznig P, Reichrath J (2011) Peroxisome proliferator-activated receptors (PPARs) in dermatology. Challenge and promise. Derm Endocrinol 3:130–135

    Article  CAS  Google Scholar 

  86. Sertznig P, Seifert M, Tilgen W, Reichrath J (2008) Peroxisome proliferator-activated receptors (PPARs) and the human skin: importance of PPARs in skin physiology and dermatologic diseases. Am J Clin Dermatol 9:15–31

    Article  PubMed  Google Scholar 

  87. Sher T, Yi HF, McBride OW, Gonzalez FJ (1993) cDNA cloning, chromosomal mapping and functional characterization of the human peroxisome proliferator activated receptor. Biochemistry 32:5598–5604

    Article  CAS  PubMed  Google Scholar 

  88. Shi-wen X, Eastwood M, Stratton RJ, Denton CP, Leask A, Abraham DJ (2010) Rosiglitazone alleviates the persistent fibrotic phenotype of lesional skin scleroderma fibroblasts. Rheumatology 49:259–263

    Article  PubMed  CAS  Google Scholar 

  89. Slama L, Lanoy E, Valantin MA, Bastard JP, Chermak A, Boutekatjirt A et al (2008) Effect of pioglitazone on HIV-1-related lipodystrophy: a randomized double-blind placebo-controlled trial (ANRS 113). Antivir Ther 13:67–76

    CAS  PubMed  Google Scholar 

  90. Smith KJ, Dipreta E, Skelton H (2001) Peroxisomes in dermatology. Part II. J Cutan Med Surg 5:315–322

    Article  CAS  PubMed  Google Scholar 

  91. Staumont-Sallé D, Abboud G, Brénuchon C, Kanda A, Roumier T, Lavogiez C et al (2008) Peroxisome proliferatoractivated receptor alpha regulates skin inflammation and humoral response in atopic dermatitis. J Allergy Clin Immunol 121:962–968

    Article  PubMed  CAS  Google Scholar 

  92. Sutinen J (2009) The Effects of thiazolidinediones on metabolic complications and lipodystrophy in HIV-infected patients. PPAR Res 2009:373524. doi:10.1155/2009/373524

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  93. Sutinen J, Hakkinen AM, Westerbacka J, Seppala-Lindroos A, Halavaara J, Jarvinen A et al (2003) Rosiglitazone in the treatment of HAART-associated lipodystrophy-a randomized double-blind placebo-controlled study. Antivir Ther 8:199–207

    CAS  PubMed  Google Scholar 

  94. Tan NS, Michalik L, Noy N, Yasmin R, Pacot C, Heim M et al (2001) Critical roles of PPAR beta/delta in keratinocyte response to inflammation. Genes Dev 15:3263–3677

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  95. Thieringer R, Fenyk-Melody JE, Le Grand CB, Shelton BA, Detmers PA, Somers EP, Carbin L et al (2000) Activation of peroxisome proliferator activated receptor gamma does not inhibit IL-6 or TNF-alpha responses of macrophages to lipopolysaccharides in vitro or in vivo. J Immunol 164:1046–1054

    Article  CAS  PubMed  Google Scholar 

  96. Thuillier P, Anchiraico GJ, Nickel KP, Maldve RE, Gimenez-Conti I, Muga SJ et al (2000) Activators of peroxisome proliferator-activated receptor-alpha partially inhibit mouse skin tumor promotion. Mol Carcinog 29:134–142

    Article  CAS  PubMed  Google Scholar 

  97. Tirado-Sanchez A, Santamaria-Roman A, Ponce-Olivera RM (2009) Efficacy of dioic acid compared with hydroquinone in the treatment of melasma. Int J Dermatol 48:893–895

    Article  PubMed  Google Scholar 

  98. Trivedi NR, Cong Z, Nelson AM, Albert AJ, Rosamilla LL, Sivarajah S et al (2006) Peroxisome proliferator-activated receptors increase human sebum production. J Invest Dermatol 2006(126):2002–2009

    Article  CAS  Google Scholar 

  99. Tyagi S, Gupta P, Saini AS, Kaushal C, Sharma S (2011) The peroxisome proliferator-activated receptor: a family of nuclear receptors role in various diseases. J Adv Pharm Technol Res 2:236–240

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  100. Vogt T, Hafner C, Bross K, Bataille F, Jauch KW, Berand A et al (2003) Antiangiogenic therapy with pioglitazone, rofecoxib and metronomic trofosfamide in patients with advanced malignant vascular tumors. Cancer 98:2251–2256

    Article  CAS  PubMed  Google Scholar 

  101. Wahli W (2002) Peroxisome proliferator-activated receptors (PPARs): from metabolic control to epidermal wound healing. Swiss Med Wkly 132:83–91

    CAS  PubMed  Google Scholar 

  102. Westergaard M, Henningsen J, Svendsen ML, Johansen C, Jensen UB, Schroder HD et al (2001) Modulation of keratinocyte gene expression and differentiation by PPAR selective ligands and tetradecylthioacetic acid. J Invest Dermatol 116:702–712

    Article  CAS  PubMed  Google Scholar 

  103. Wiechers JW, Rawlings AV, Garcia C, Chesne C, Balaguer P, Corre S et al (2005) A new mechanism of action for skin whitening agents: binding to the peroxisome proliferators-activated receptor. Int J Cosmet Sci 27:123–132

    Article  CAS  PubMed  Google Scholar 

  104. Wróbel A, Seltmann H, Fimmel S, Müller-Decker K, Tsukada M, Bogdanoff B et al (2003) Differentiation and apoptosis in human immortalized sebocytes. J Invest Dermatol 120:175–181

    Article  PubMed  Google Scholar 

  105. Wu M, Melichian DS, Chang E, Warner-Blankenship M, Ghosh AK, Varga J (2009) Rosiglitazone abrogates bleomycin-induced scleroderma and blocks profibrotic responses through peroxisome proliferator activated receptor-gamma. Am J Pathol 174:519–533

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  106. Xin X, Yang S, Kowalski J, Gerritsen ME (1999) Peroxisome proliferator-activated receptor gamma ligands are potent inhibitors of angiogenesis in vitro and in vivo. J Biol Chem 274:9116–9121

    Article  CAS  PubMed  Google Scholar 

  107. Yang Y, Lovett-Racke AE, Racke MK (2010) Regulation of immune responses and autoimmune encephalomyelitis by PPARs. PPAR Res. doi:10.1155/2010/104705

    Google Scholar 

  108. Yessofou A, Wahli W (2010) Multifaceted roles of peroxisome proliferator-activated receptors (PPARs) at the cellular and whole organism levels. Swiss Med Wkly 140:w13071

    Google Scholar 

  109. Yilmaz M, Karakoc A, Toruner FB, Cakir N, Tiras B, Ayvaz G et al (2005) The effects of rosiglitazone and metformin on menstrual cyclicity and hirsutism in polycystic ovary syndrome. Gynecol Endocrinol 21:154–160

    Article  CAS  PubMed  Google Scholar 

  110. Zoete V, Grosdidier A, Michielin O (2007) Peroxisome proliferator activated receptor structures: ligand specificity, molecular switch and interactions with regulators. Biochem Biophys Acta 1771:915–925

    CAS  PubMed  Google Scholar 

  111. Zouboulis CC (2009) Zileuton, a new efficient and safe systemic anti-acne drug. Dermatoendocrinol 1:188–192

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

Authors declare no conflict of interest. The authors alone are responsible for the content and writing of the paper.

Author information

Authors and Affiliations

  1. Department of Dermatology, Venereology and Leprosy, Dr. R. P. Govt. Medical College, Kangra, Tanda, 176001, Himachal Pradesh, India

    Mrinal Gupta, Vikram K. Mahajan, Karaninder S. Mehta, Pushpinder S. Chauhan & Ritu Rawat

Authors
  1. Mrinal Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vikram K. Mahajan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Karaninder S. Mehta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pushpinder S. Chauhan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ritu Rawat
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vikram K. Mahajan.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gupta, M., Mahajan, V.K., Mehta, K.S. et al. Peroxisome proliferator-activated receptors (PPARs) and PPAR agonists: the ‘future’ in dermatology therapeutics?. Arch Dermatol Res 307, 767–780 (2015). https://doi.org/10.1007/s00403-015-1571-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-015-1571-1

Keywords

Search

Navigation