Troglitazone Improves Psoriasis and Normalizes Models of Proliferative Skin Disease

Ellis, Charles N.; Varani, James; Fisher, Gary J.; Zeigler, Mary E.; Pershadsingh, Harrihar A.; Benson, Stephen C.; Chi, Yiqing; Kurtz, Theodore W.

doi:10.1001/archderm.136.5.609

Cited by 197 publications

(66 citation statements)

References 48 publications

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“…PPARα expression was not detectable by this method, but was detectable by reverse transcriptase-polymerase chain reaction (RT-PCR) over time in culture. In addition, PPARγ (both γ1 and γ2) could be detected by RT-PCR after inducing keratinocyte differentiation by shifting to a high calcium medium, a finding which has been confirmed [33]. Remarkably, the specific ligand BRL did not cause reporter gene transactivation of endogenous PPARγ; the possibility that the culture medium was not optimal for keratinocyte differentiation during this experiment cannot be ruled out from the data.…”

Section: Ppar Gene Expression In Normal Skinsupporting

confidence: 56%

“…PPARγ immunofluorescence was found in human keratinocytes cultured under differentiating conditions (high calcium medium) [33]. One preliminary study found immunohistochemical expression of all the PPAR subtypes in facial skin sections [34].…”

Section: Ppar Gene Expression In Normal Skinmentioning

confidence: 99%

“…However, in nonspecifically inflamed epidermis our preliminary studies show abundant PPARγ immunostaining. Further investigation of the role of PPARγ in epidermis was prompted by the serendipitous finding that thiazolidinediones improve psoriasis and the discovery that thiazolidinediones can inhibit proliferation of a variety of malignant and nonmalignant tissues [33]. PPARγ ligands were found to inhibit the proliferation of cultured normal and psoriatic human keratinocytes, as well as to reduce epidermal hyperplasia in organ culture and skin transplant models of psoriasis.…”

Section: Evidence For Ppar Effects On Proliferative and Inflammatory mentioning

confidence: 99%

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Peroxisome Proliferator-Activated Receptors and Skin Development

2000

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PPARs are nuclear hormone receptors. PPAR subtypes (α, γ, δ, the latter a xPPARβ homologue) were initially investigated in skin because of their known role in regulating lipid metabolism. Studies adding specific PPAR ligand activators to cultured skin or skin cells are compatible with the concepts that PPARα activation mediates early lipogenic steps common to the function of both skin epidermal cells (keratinocytes) and sebaceous cells (sebocytes), PPARγ activation plays a unique role in stimulating sebocyte lipogenesis, and PPARδ activation may contribute to lipid biosynthesis in both sebocytes and keratinocytes under certain circumstances. Epidermal keratinocytes appear to express small amounts of PPARα and PPARδ mRNA and a trace of PPARγ mRNA which is up-regulated with differentiation. Sebocytes express all subtypes; PPARγ gene expression excedes that in epidermis. The emerging data on PPAR protein expression suggests that epidermis normally expresses predominantly PPARα, while sebocytes express more PPARγ than PPARα. These expression patterns may change during hyperplasia, differentiation and inflammation. Gene disruption studies in mice are compatible with a contribution of PPARα to skin barrier function, suggest that PPARγ is necessary for sebocyte differentiation, and indicate that PPARδ can ameliorate inflammatory responses in skin. PPARs appear to play a role in keratinocyte synthesis of the lipids that they export to the intercellular space to form the skin permeability barrier. They also appear to be important for sebocyte formation of the intracellular fused lipid droplets that constitute the holocrine secretion of the sebaceous gland. In addition, they may play roles in keratinocyte growth and differentiation and the inhibition of skin inflammation by diverse mechanisms not necessarily related to fat metabolism.

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Section: Ppar Gene Expression In Normal Skinsupporting

confidence: 56%

Section: Ppar Gene Expression In Normal Skinmentioning

confidence: 99%

Section: Evidence For Ppar Effects On Proliferative and Inflammatory mentioning

confidence: 99%

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Peroxisome Proliferator-Activated Receptors and Skin Development

2000

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“…The expression of CD36 in human keratinocytes is induced by treatment with ligands of each PPAR subtype. Administration of the formerly available PPARg agonist troglitazone to patients improved psoriasis and inhibited keratinocyte proliferation, suggesting that this class of drugs may be beneficial in treating diseases of the skin (64).…”

Section: Peroxisome Proliferator-activated Receptorsmentioning

confidence: 99%

Thematic review series: Skin Lipids. Sebaceous gland lipids: friend or foe?

Smith

Thiboutot

2008

Journal of Lipid Research

319

289

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Sebaceous glands are intriguing glands that are found throughout the human body except on the palms of the hands and soles of the feet. The true function of these glands has yet to be determined, but there are several theories, including antioxidant effects, antibacterial effects, and transport of pheromones. Sebaceous glands produce lipids that are involved in the pathogenesis of one of the most prevalent diseases of adolescence, acne. Although the majority of lipids produced by the sebaceous gland are also produced in other areas of the body, there are two that are characteristic of the sebaceous gland, wax esters and squalene.This review seeks to present an update on the physiology of the sebaceous glands, with particular emphasis on the production of sebaceous lipids.

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“…Induction of PPARα and PPARγ expression is linked to differentiation, and accordingly, is confined to suprabasal keratinocytes. PPARδ and PPARγ inhibition resulted in a dramatic decrease in proliferation and a robust up-regulation of the expression of involucrin and transglutaminase [104, 105]. Preliminary results have shown expression of PPARδ and PPARγ in the human sebaceous gland [106, 107].…”

Section: Biological Activity Of Hormones In Human Skinmentioning

confidence: 99%

Human Skin: An Independent Peripheral Endocrine Organ

2000

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The historical picture of the endocrine system as a set of discrete hormone-producing organs has been substituted by organs regarded as organized communities in which the cells emit, receive and coordinate molecular signals from established endocrine organs, other distant sources, their neighbors, and themselves. In this wide sense, the human skin and its tissues are targets as well as producers of hormones. Although the role of hormones in the development of human skin and its capacity to produce and release hormones are well established, little attention has been drawn to the ability of human skin to fulfil the requirements of a classic endocrine organ. Indeed, human skin cells produce insulin-like growth factors and -binding proteins, propiomelanocortin derivatives, catecholamines, steroid hormones and vitamin D from cholesterol, retinoids from diet carotenoids, and eicosanoids from fatty acids. Hormones exert their biological effects on the skin through interaction with high-affinity receptors, such as receptors for peptide hormones, neurotransmitters, steroid hormones and thyroid hormones. In addition, the human skin is able to metabolize hormones and to activate and inactivate them. These steps are overtaken in most cases by different skin cell populations in a coordinated way indicating the endocrine autonomy of the skin. Characteristic examples are the metabolic pathways of the corticotropin-releasing hormone/propiomelanocortin axis, steroidogenesis, vitamin D, and retinoids. Hormones exhibit a wide range of biological activities on the skin, with major effects caused by growth hormone/insulin-like growth factor-1, neuropeptides, sex steroids, glucocorticoids, retinoids, vitamin D, peroxisome proliferator-activated receptor ligands, and eicosanoids. At last, human skin produces hormones which are released in the circulation and are important for functions of the entire organism, such as sex hormones, especially in aged individuals, and insulin-like growth factor-binding proteins. Therefore, the human skin fulfils all requirements for being the largest, independent peripheral endocrine organ.

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Troglitazone Improves Psoriasis and Normalizes Models of Proliferative Skin Disease

Cited by 197 publications

References 48 publications

Peroxisome Proliferator-Activated Receptors and Skin Development

Peroxisome Proliferator-Activated Receptors and Skin Development

Thematic review series: Skin Lipids. Sebaceous gland lipids: friend or foe?

Human Skin: An Independent Peripheral Endocrine Organ

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