Development of new 3D human ex vivo models to study sebaceous gland lipid metabolism and modulations

Bengy, Anne-France de; Forraz, Nico; Danoux, Louis; Berthélémy, Nicolas; Cadau, Sébastien; Degoul, Olivier; Andre, Valérie; Pain, Stéphanie; McGuckin, Colin

doi:10.1111/cpr.12524

Cited by 10 publications

(11 citation statements)

References 36 publications

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“…The fields of neuroendocrinology and neurobiology are conceptually similar, in terms of the release of factors from neurons into the extracellular milieu (Goyal & Chaudhury, ). Therefore, we will discuss clinical evidence for neuroendocrine and neurobiological control of SGs alongside experimental data acquired in vivo , or through sebocyte culture systems (Ehrmann & Schneider, ; Schneider & Zouboulis, ; de Bengy et al ., ). We still make a distinction in our discussions between hormones and regulatory factors typically considered part of the neuroendocrine system, and those associated with the peripheral nervous system [e.g.…”

Section: Relevance Of the Brain–sebaceous Gland Axis To Skin Physiolomentioning

confidence: 97%

Neuroendocrinology and neurobiology of sebaceous glands

et al. 2020

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The nervous system communicates with peripheral tissues through nerve fibres and the systemic release of hypothalamic and pituitary neurohormones. Communication between the nervous system and the largest human organ, skin, has traditionally received little attention. In particular, the neuro-regulation of sebaceous glands (SGs), a major skin appendage, is rarely considered. Yet, it is clear that the SG is under stringent pituitary control, and forms a fascinating, clinically relevant peripheral target organ in which to study the neuroendocrine and neural regulation of epithelia. Sebum, the major secretory product of the SG, is composed of a complex mixture of lipids resulting from the holocrine secretion of specialised epithelial cells (sebocytes). It is indicative of a role of the neuroendocrine system in SG function that excess circulating levels of growth hormone, thyroxine or prolactin result in increased sebum production (seborrhoea). Conversely, growth hormone deficiency, hypothyroidism, and adrenal insufficiency result in reduced sebum production and dry skin. Furthermore, the androgen sensitivity of SGs appears to be under neuroendocrine control, as hypophysectomy (removal of the pituitary) renders SGs largely insensitive to stimulation by testosterone, which is crucial for maintaining SG homeostasis. However, several neurohormones, such as adrenocorticotropic hormone and α-melanocyte-stimulating hormone, can stimulate sebum production independently of either the testes or the adrenal glands, further underscoring the importance of neuroendocrine control in SG biology. Moreover, sebocytes synthesise several neurohormones and express their receptors, suggestive of the presence of neuro-autocrine mechanisms of sebocyte modulation. Aside from the neuroendocrine system, it is conceivable that secretion of neuropeptides and neurotransmitters from cutaneous nerve endings may also act on sebocytes or their progenitors, given that the skin is richly innervated. However, to date, the neural controls of SG development and function remain poorly investigated and incompletely understood. Botulinum toxin-mediated or facial paresis-associated reduction of human sebum secretion suggests that cutaneous nerve-derived substances modulate lipid and inflammatory cytokine synthesis by sebocytes, possibly implicating the nervous system in acne pathogenesis. Additionally, evidence suggests that cutaneous denervation in mice alters the expression of key regulators of SG homeostasis. In this review, we examine the current evidence regarding neuroendocrine and neurobiological regulation of human SG function in physiology and pathology. We further call attention to this line of research as an instructive model for probing and therapeutically manipulating the mechanistic links between the nervous system and mammalian skin.

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Section: Relevance Of the Brain–sebaceous Gland Axis To Skin Physiolomentioning

confidence: 97%

Neuroendocrinology and neurobiology of sebaceous glands

et al. 2020

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“…During maturation, MYC expression decreases, and SG proliferative cells progressively migrate and differentiate into the inner mass, from an early stage over middle stage to terminal differentiation, accumulating lipid droplets and eventually bursting to release lipids into the sebaceous duct. The early-stage differentiation markers are keratin 7 (K7) ( de Bengy et al, 2019 ) and androgen receptor (AR) ( Cottle et al, 2013 ). AR is highly expressed in the middle stage as well, and peroxisome proliferator-activated receptor gamma (PPARγ) and fatty acid synthase (FASN) are regarded as markers of middle-stage differentiation ( Cottle et al, 2013 ).…”

Section: Stem Cells Development and Differentiation Of Sebaceous Glandsmentioning

confidence: 99%

“…AR is highly expressed in the middle stage as well, and peroxisome proliferator-activated receptor gamma (PPARγ) and fatty acid synthase (FASN) are regarded as markers of middle-stage differentiation ( Cottle et al, 2013 ). Terminally differentiated and mature sebocytes are oil red O ( Feldman et al, 2019 ), melanocortin 5 receptor (MC5R), and mucin 1 (MUC-1) ( Hinde et al, 2013 ; de Bengy et al, 2019 ), also known as the epithelial membrane antigen (EMA) and are adipophilin-positive ( Hinde et al, 2013 ). Remarkably, K7 and MUC-1 are sebaceous markers in humans but not in murine SGs ( Hinde et al, 2013 ).…”

Section: Stem Cells Development and Differentiation Of Sebaceous Glandsmentioning

confidence: 99%

Aging in the sebaceous gland

Hou

Wei

Zouboulis

et al. 2022

Front. Cell Dev. Biol.

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Sebaceous glands (SGs) originate from hair follicular stem cells and secrete lipids to lubricate the skin. The coordinated effects of intrinsic and extrinsic aging factors generate degradation of SGs at a late age. Senescence of SGs could be a mirror of the late aging of both the human body and skin. The procedure of SG aging goes over an initial SG hyperplasia at light-exposed skin areas to end with SG atrophy, decreased sebum secretion, and altered sebum composition, which is related to skin dryness, lack of brightness, xerosis, roughness, desquamation, and pruritus. During differentiation and aging of SGs, many signaling pathways, such as Wnt/β-catenin, c-Myc, aryl hydrocarbon receptor (AhR), and p53 pathways, are involved. Random processes lead to random cell and DNA damage due to the production of free radicals during the lifespan and neuroendocrine system alterations. Extrinsic factors include sunlight exposure (photoaging), environmental pollution, and cigarette smoking, which can directly activate signaling pathways, such as Wnt/β-catenin, Notch, AhR, and p53 pathways, and are probably associated with the de-differentiation and hyperplasia of SGs, or indirectly activate the abovementioned signaling pathways by elevating the inflammation level. The production of ROS during intrinsic SG aging is less, the signaling pathways are activated slowly and mildly, and sebocytes are still differentiated, yet terminal differentiation is not completed. With extrinsic factors, relevant signaling pathways are activated rapidly and fiercely, thus inhibiting the differentiation of progenitor sebocytes and even inducing the differentiation of progenitor sebocytes into keratinocytes. The management of SG aging is also mentioned.

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“…Obviously, the long‐term cultivation of intact SGs would be a good model to study SG physiology and patho‐physiology in vitro. Based on previous experiments, the cultivation and maintenance of human SGs ex vivo for up to 6 weeks was demonstrated applying an “air‐liquid” and “sandwich” 3D protocol 61,71,72 . This particular method will allow studying the metabolism, lipid production, inflammatory processes, hormone and growth factor regulation of human SGs in 3D as well as progenitor cell contribution to the maintenance and maturation of the glands (Figure 3D).…”

Section: Sebaceous Gland Stem Cells In Vitro and Organoid Culturesmentioning

confidence: 99%

Stem and progenitor cells in sebaceous gland development, homeostasis and pathologies

Geueke

Niemann

2021

Experimental Dermatology

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Sebaceous glands (SGs) are acinar holocrine-secreting appendages of the epidermis and localize to most areas of the body surface. 1 Generally, SGs constitute a crucial component of the pilosebaceous unit and are intimately associated with the junctional zone (JZ), an area of the upper and permanent part of the hair follicle (HF). While the outer layer of the SG contains proliferative cells, the inner compartment is composed of sebocytes, specialized keratinocytes, that produce a mixture of an oily and waxy material, called sebum. [1][2][3] Upon differentiation and maturation of sebocytes, the lipidcontaining sebum is released by holocrine secretion through a specialized secretory duct of the gland into the follicular canal to reach the surface of the skin. 4 This complex mixture of lipids contributes significantly to the barrier function of mammalian skin by reducing water loss from the surface of the skin and facilitates water repulsion and thermoregulation. 1,5 Although all the details of the physiological complexity of SGs are not completely understood, sebum has antimicrobial activity, contains antioxidants and protects against UVB-induced apoptosis. 1,4,[6][7][8] Distinct regions of the skin and surface epithelium generate SGs independently from HF structures, e.g.

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Development of new 3D human ex vivo models to study sebaceous gland lipid metabolism and modulations

Cited by 10 publications

References 36 publications

Neuroendocrinology and neurobiology of sebaceous glands

Neuroendocrinology and neurobiology of sebaceous glands

Aging in the sebaceous gland

Stem and progenitor cells in sebaceous gland development, homeostasis and pathologies

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