Delayed Hair Follicle Morphogenesis and Hair Follicle Dystrophy in a Lipoatrophy Mouse Model of Pparg Total Deletion

Sardella, Chiara; Winkler, Carine; Quignodon, Laure; Hardman, Jonathan A.; Toffoli, Barbara; Attianese, Greta Maria Paola Giordano; Hundt, Jennifer E.; Michalik, Liliane; Vinson, Charles; Paus, Ralf; Desvergne, Béatrice; Gilardi, Federica

doi:10.1016/j.jid.2017.09.024

Cited by 44 publications

(64 citation statements)

References 63 publications

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“…Diabetics treated with PPARγ ligands exhibit increased sebum secretion, and these same compounds increase lipid production and sensitivity to testosterone in SZ95 and SEB‐1 sebocytes . Loss of PPARγ in mice results in SG atrophy, loss of sebum and scarring alopecia …”

Section: Factors Controlling Sebaceous Gland Homeostasismentioning

confidence: 99%

Homeostasis of the sebaceous gland and mechanisms of acne pathogenesis

et al. 2019

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Summary Background Sebaceous glands (SGs) are appendages of mammalian skin that produce a mixture of lipids known as sebum. Acne vulgaris is an exceptionally common skin condition, characterized by elevated sebum production, altered sebum composition, and the formation of infundibular cysts, called comedones. Comedo‐associated SGs are atrophic, suggesting that comedo formation involves abnormal differentiation of progenitor cells that generate the SG and infundibulum: the ‘comedo switch’. Understanding the biological processes that govern SG homeostasis promises to highlight potential aetiological mechanisms underlying acne and other SG‐associated skin disorders. Results In this review, we discuss the clinical data, genetic mouse models and in vitro research that have highlighted major hormones, paracrine factors, transcription factors and signalling pathways that control SG homeostasis. These include, but are not limited to androgens, progestogens and oestrogens; retinoids; receptor tyrosine kinases such as ErbB family receptors, fibroblast growth factor receptor 2 and insulin/insulin‐like growth factor 1 receptors; peroxisome proliferator‐activated receptor γ; aryl hydrocarbon receptor; and the Wnt signalling pathway. Where possible, the cellular and molecular mechanisms by which these regulatory factors control SG biology are indicated, along with considerations as to how they might contribute to acne pathogenesis. Conclusions Future research should seek to establish the relative importance, and causative relationships, of altered sebum production, sebum composition, inflammation and abnormal differentiation of sebaceous progenitors to the process of comedo formation in acne. Such an understanding will allow for therapeutic targeting of regulatory factors that control SG homeostasis, with the aim of treating acne.

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Section: Factors Controlling Sebaceous Gland Homeostasismentioning

confidence: 99%

Homeostasis of the sebaceous gland and mechanisms of acne pathogenesis

et al. 2019

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“…Since all PPARs are widely expressed in human skin and its appendages, there is increasing interest in their role in maintaining cutaneous homeostasis and in dermatological disorders . PPAR‐mediated signalling has attracted special interest in psoriasis, atopic dermatitis, acne, skin ageing, scleroderma, melasma, lipodystrophy and skin cancer . In the context of this Focus Theme Issue , this development encourages one to also take a closer look at why and how exactly PPARs are of special interest in a translational hair research context, with a strict focus on their best‐investigated isoform, PPAR‐γ.…”

Section: Ppars In Human Biology and Skinmentioning

confidence: 99%

“…Strikingly, Karnik et al also showed that PPAR‐γ signalling is crucial for HFeSC survival in mice by demonstrating that the keratin 15 (K15) promoter‐targeted deletion of this receptor in these stem cells leads to a scarring alopecia‐like loss of HFs . Constitutive, generalized knockout of PPAR‐γ in mice also induces perifollicular inflammatory cell infiltrates and atrophy of the PSU, resulting in a scarring alopecia‐like phenotype . With this seminal work, PPAR‐γ came onto the radar of translational hair research, even though a later, laser capture microdissection‐based gene expression analysis found no significant difference in PPAR‐γ expression between lesional and non‐lesional bulge epithelium of the same LPP patient .…”

Section: The Importance Of Ppar‐γ For the Bulge Stem Cells And Its Rementioning

confidence: 99%

“…The field of PPAR and skin has received a lot of attention in recent years, and although many studies using in vitro, ex vivo and in vivo models have been performed, there are still many open questions to be answered. Selected research frontiers are listed below: PPAR‐γ knocked‐our models showed in addition to scarring alopecia‐like phenotype also dystrophy of the SGs and lipoatrophy . Since dermal white adipose tissue may be involved in the regulation of HF morphogenesis, it is still unclear whether knocking ‐ out PPAR‐γ leads to inflammation and hair loss directly because of the resulting uncontrolled chronic inflammation, or due to the lack of supporting adipose tissue and functioning SGs .…”

Section: Challenges and Future Perspectivesmentioning

confidence: 99%

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PPAR‐γ signalling as a key mediator of human hair follicle physiology and pathology

Ramot

Bertolini

Boboljova

et al. 2019

Experimental Dermatology

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Peroxisome proliferator‐activated receptors (PPARs) are abundantly expressed in human skin, with PPAR‐γ being the most intensively investigated isoform. In various ex vivo and in vivo models, PPAR‐γ‐mediated signalling has recently surfaced as an essential element of hair follicle (HF) development, growth and stem cell biology. Moreover, the availability of novel, topically applicable PPAR‐γ modulators with a favourable toxicological profile has extended the range of potential applications in clinical dermatology. In this review, we synthesize where this field currently stands and sketch promising future research avenues, focussing on the role of PPAR‐γ‐mediated signalling in the biology and pathology of human scalp HFs, with special emphasis on scarring alopecias such as lichen planopilaris and frontal fibrosing alopecia as model human epithelial stem cell diseases. In particular, we discuss whether and how pharmacological modulation of PPAR‐γ signalling may be employed for the management of hair growth disorders, for example, in scarring alopecia (by reducing HF inflammation as well as by promoting the survival and suppressing pathological epithelial‐mesenchymal transition of keratin 15 + epithelial stem cells in the bulge) and in hirsutism/hypertrichosis (by promoting catagen development). Moreover, we explore the potential role of PPAR‐γ in androgenetic alopecia, HF energy metabolism and HF ageing, and consider clinical perspectives that emanate from the limited data available on this so far. As this field of translational human hair research is still in its infancy, many open questions exist, for which we briefly delineate selected experimental approaches that promise to generate instructive answers in the near future.

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“…Hair follicles develop at the interaction sites between embryonic epidermis and papillary fibroblast progenitor cells. (b) During E17.5 to E18.5, development of hair follicles and dWAT are coupled 4,41,44,45,110 . Enlarged hair follicles activate several pro-adipogenic signalling pathways, including Hedgehog 45 and Bmp 48 .…”

Section: Figurementioning

confidence: 99%

Emerging nonmetabolic functions of skin fat

Guerrero‐Juarez

Plikus

2018

Nat Rev Endocrinol

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Although the major white adipose depots evolved primarily to store energy, secrete hormones and thermo-insulate the body, multiple secondary depots developed additional specialized and unconventional functions. Unlike any other fat tissue, dermal white adipose tissue (dWAT) evolved a large repertoire of novel features that are central to skin physiology, which we discuss in this Review. dWAT exists in close proximity to hair follicles, the principal appendages of the skin that periodically grow new hairs. Responding to multiple hair-derived signals, dWAT becomes closely connected to cycling hair follicles and periodically cycles itself. At the onset of new hair growth, hair follicles secrete activators of adipogenesis, while at the end of hair growth, a reduction in the secretion of activators or potentially, an increase in the secretion of inhibitors of adipogenesis, results in fat lipolysis. Hair-driven cycles of dWAT remodelling are uncoupled from size changes in other adipose depots that are controlled instead by systemic metabolic demands. Rich in growth factors, dWAT reciprocally signals to hair follicles, altering the activation state of their stem cells and modulating the pace of hair regrowth. dWAT cells also facilitate skin repair following injury and infection. In response to wounding, adipose progenitors secrete repair-inducing activators, while bacteria-sensing adipocytes produce antimicrobial peptides, thus aiding innate immune responses in the skin.

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Delayed Hair Follicle Morphogenesis and Hair Follicle Dystrophy in a Lipoatrophy Mouse Model of Pparg Total Deletion

Cited by 44 publications

References 63 publications

Homeostasis of the sebaceous gland and mechanisms of acne pathogenesis

Homeostasis of the sebaceous gland and mechanisms of acne pathogenesis

PPAR‐γ signalling as a key mediator of human hair follicle physiology and pathology

Emerging nonmetabolic functions of skin fat

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