Peroxisome proliferator-activated receptor and farnesoid X receptor ligands differentially regulate sebaceous differentiation in human sebaceous gland organ cultures in vitro

Downie, M.M.T.; Sanders, Deborah A.; Maier, Lisa M.; Stock, D.M.; Kealey, Terence

doi:10.1111/j.1365-2133.2004.06171.x

Cited by 67 publications

(64 citation statements)

References 38 publications

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“…These findings indicate that EGCG can overcome the stimulatory effects of IGF-I, and Akt, mTOR and S6 may be a suitable anti-IGF-I agent. In a previous study, mTOR signaling regulated peroxisome proliferator-activated receptor-g (Kim and Chen, 2004), which is known to have major regulatory roles in the differentiation of sebocytes and lipid production (Chen et al, 2003;Downie et al, 2004;Trivedi et al, 2006). However, the precise mechanism by which EGCG inhibits activation of receptor Y kinase remains to be determined.…”

Section: Discussionmentioning

confidence: 95%

Epigallocatechin-3-Gallate Suppresses IGF-I-Induced Lipogenesis and Cytokine Expression in SZ95 Sebocytes

Kim

Sohn

et al. 2012

Journal of Investigative Dermatology

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Acne vulgaris is the most common disease of the pilosebaceous unit. The pathogenesis of this inflammatory disease is complex, involving increased sebum production and perifollicular inflammation. To identify effective agents for factors that induce acne vulgaris, we explored the pharmacological potential of epigallocatechin-3-gallate (EGCG), which has been widely investigated as an anti-proliferative and anti-inflammatory agent. In this study, we demonstrated that topical application of EGCG to rabbit auricles reduced the size of the sebaceous glands. When applied to cultured human SZ95 sebocytes, EGCG strongly suppressed cell proliferation and lipogenesis. These actions of EGCG were reproduced in IGF-I-differentiated SZ95 sebocytes. To investigate the anti-inflammatory potential of EGCG, we evaluated pro-inflammatory cytokine synthesis in IGF-I-differentiated SZ95 sebocytes and found that expression of IL-1, IL-6, and IL-8 was decreased. These results provide early evidence that EGCG is an effective candidate for acne therapy whose mechanisms of action in IGF-I-differentiated SZ95 sebocytes include the inhibition of lipogenesis and inflammation.

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Section: Discussionmentioning

confidence: 95%

Epigallocatechin-3-Gallate Suppresses IGF-I-Induced Lipogenesis and Cytokine Expression in SZ95 Sebocytes

Kim

Sohn

et al. 2012

Journal of Investigative Dermatology

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“…In monolayer cultures of sebocytes, PPAR agonists stimulate lipogenesis (Trivedi et al, 2006), whereas treatment of the intact gland inhibits sebum production (Downie et al, 2004). Scd1 has been shown to contain a PPAR response element in its promoter (Miller and Ntambi, 1996), and hence the lack of PPARg and Scd1 in the sebaceous glands of Gsdma3 Dfl / þ mice does point toward a role for PPARg in promoting lipogenesis in the sebaceous gland.…”

Section: Discussionmentioning

confidence: 98%

Delineating Immune-Mediated Mechanisms Underlying Hair Follicle Destruction in the Mouse Mutant Defolliculated

Ruge

Glavini

Gallimore

et al. 2011

Journal of Investigative Dermatology

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Defolliculated (Gsdma3(Dfl)/+) mice have a hair loss phenotype that involves an aberrant hair cycle, altered sebaceous gland differentiation with reduced sebum production, chronic inflammation, and ultimately the loss of the hair follicle. Hair loss in these mice is similar to that seen in primary cicatricial, or scarring alopecias in which immune targeting of hair follicle stem cells has been proposed as a key factor resulting in permanent hair follicle destruction. In this study we examine the mechanism of hair loss in GsdmA3(Dfl)/+ mice. Aberrant expression patterns of stem cell markers during the hair cycle, in addition to aberrant behavior of the melanocytes leading to ectopic pigmentation of the hair follicle and epidermis, indicated the stem cell niche was not maintained. An autoimmune mechanism was excluded by crossing the mice with rag1-/- mice. However, large numbers of macrophages and increased expression of ICAM-1 were still present and may be involved either directly or indirectly in the hair loss. Reverse transcriptase-PCR (RT-PCR) and immunohistochemistry of sebaceous gland differentiation markers revealed reduced peroxisome proliferator-activated receptor-γ (PPARγ), a potential cause of reduced sebum production, as well as the potential involvement of the innate immune system in the hair loss. As reduced PPARγ expression has recently been implicated as a cause for lichen planopilaris, these mice may be useful for testing therapies.

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“…Although there is little expression in the dermis in vivo, constitutive expression has been reported for PPARg, LXRa, and LXRb in cultured fibroblasts (20,21). Furthermore, strong expression of PPARa, PPARb/y, PPARg1, LXRa, and LXRb is present in sebaceous glands (22)(23)(24)(25)(26). LXRa and LXRb are also expressed in sweat gland epithelia.…”

Section: Ppar and Lxr Expression In The Skinmentioning

confidence: 97%

Thematic Review Series: Skin Lipids. Peroxisome proliferator-activated receptors and liver X receptors in epidermal biology

Schmuth

Jiang

Dubrac

et al. 2008

Journal of Lipid Research

184

160

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The epidermis is a very active site of lipid metabolism, and all peroxisome proliferator-activated receptor (PPAR) and liver X receptor (LXR) isoforms are expressed in the epidermis. Activation of PPARa, -b/d, or -g or LXRs stimulates keratinocyte differentiation. Additionally, activation of these receptors also improves permeability barrier homeostasis by a number of mechanisms, including stimulating epidermal lipid synthesis, increasing lamellar body formation and secretion, and increasing the activity of enzymes required for the extracellular processing of lipids in the stratum corneum, leading to the formation of lamellar membranes that mediate permeability barrier function. The stimulation of keratinocyte differentiation and permeability barrier formation also occurs during fetal development, resulting in accelerated epidermal development. PPAR and LXR activation regulates keratinocyte proliferation and apoptosis, and studies have shown that these receptors play a role in cutaneous carcinogenesis. Lastly, PPAR and LXR activation is anti-inflammatory, reducing inflammation in animal models of allergic and irritant contact dermatitis. Because of their broad profile of beneficial effects on skin homeostasis, PPAR and LXR have great potential to serve as drug targets for common skin diseases such as psoriasis, atopic dermatitis, and skin

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Peroxisome proliferator-activated receptor and farnesoid X receptor ligands differentially regulate sebaceous differentiation in human sebaceous gland organ cultures in vitro

Cited by 67 publications

References 38 publications

Epigallocatechin-3-Gallate Suppresses IGF-I-Induced Lipogenesis and Cytokine Expression in SZ95 Sebocytes

Epigallocatechin-3-Gallate Suppresses IGF-I-Induced Lipogenesis and Cytokine Expression in SZ95 Sebocytes

Delineating Immune-Mediated Mechanisms Underlying Hair Follicle Destruction in the Mouse Mutant Defolliculated

Thematic Review Series: Skin Lipids. Peroxisome proliferator-activated receptors and liver X receptors in epidermal biology

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