Aberrant Wnt Signaling Induces Comedo-Like Changes in the Murine Upper Hair Follicle

Shang, Wei; Tan, Alvin Yong Quan; Steensel, Maurice A. M. Van; Lim, Xinhong

doi:10.1016/j.jid.2021.11.034

Cited by 4 publications

(6 citation statements)

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“…LGR5, a surface-expressed marker of adult stem cell populations in HF, participates in the maintenance and regulation of Wnt signaling via its association with Wnt receptors and mediating Wnt agonists (R-spondins, ligands for LGR5) [9,37]. In mice, Lgr5 and Lgr6 exhibit restricted, yet non-overlapping expression patterns in resting adult hair follicles: Lgr5+ cells contribute progeny to all hair follicle components (excluding the sebaceous gland), whereas Lgr6+ cells contribute exclusively differentiated progeny to the sebaceous gland and interfollicular epidermis over entire lifetime [37].…”

Section: Discussionmentioning

confidence: 99%

“…Dysfunctional progenitors (inability to migrate, abnormal cell division and lack of differentiation) will result in cells remaining in the junctional zone, causing it to expand, thus giving rise to comedones. Due to the defect in cellular motility, the SGs are not replenished and will become atrophic [8,9]. The pathogenesis of acne inflammation is still not fully understood, although certain C. acnes phylotypes (IA1) or lack of microbial diversity might trigger the responses from immune system [10].…”

Section: Introductionmentioning

confidence: 99%

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Genome-wide meta-analysis identifies novel loci conferring risk of acne vulgaris

et al. 2023

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Acne vulgaris is a common chronic skin disorder presenting with comedones, cystic structures forming within the distal hair follicle, and in most cases additionally with inflammatory skin lesions on the face and upper torso. We performed a genome-wide association study and meta-analysis of data from 34,422 individuals with acne and 364,991 controls from three independent European-ancestry cohorts. We replicated 19 previously implicated genome-wide significant risk loci and identified four novel loci [11q12.2 (FADS2), 12q21.1 (LGR5), 17q25.3 (FASN), and 22q12.1 (ZNRF3-KREMEN1)], bringing the total number of reported acne risk loci to 50. Our meta-analysis results explain 9.4% of the phenotypic variance of acne. A polygenic model of acne risk variants showed that individuals in the top 5% of the risk percentiles had a 1.62-fold (95% CI 1.47–1.78) increased acne risk relative to individuals with average risk (20–80% on the polygenic risk score distribution). Our findings highlight the Wnt and MAPK pathways as key factors in the genetic predisposition to acne vulgaris, together with the effects of genetic variation on the structure and maintenance of the hair follicle and pilosebaceous unit. Two novel loci, 11q12.2 and 17q25.3, contain genes encoding key enzymes involved in lipid biosynthesis pathways.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genome-wide meta-analysis identifies novel loci conferring risk of acne vulgaris

et al. 2023

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“…The Wnt/β-catenin pathway, an important pathway in regulating epidermal differentiation, increases the expressions of involucrin and cornifin in SGs, reduces the number of terminally differentiated sebocytes, downregulates sebum secretion, and is related to epidermal cyst formation ( Lo Celso et al, 2008 ; Shang et al, 2021 ). Loss of β-catenin in mouse epidermis leads to the enlargement of SGs ( Niemann et al, 2002 ; Lien et al, 2014 ).…”

Section: Molecular Variations Associated With Sebaceous Gland Agingmentioning

confidence: 99%

“…The expression trend of Hh was consistent with that of β-catenin ( Gat et al, 1998 ; Huelsken et al, 2001 ). Using the Hh inhibitor could reduce the cystic structures caused by aberrant activation of the Wnt-β-catenin signaling pathway ( Shang et al, 2021 ). The Hh pathway also plays a vital role in basal cell carcinoma pathogenesis ( Fania et al, 2020 ).…”

Section: Molecular Variations Associated With Sebaceous Gland Agingmentioning

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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“…This process, which has been named the "comedone switch", 3,10 involves a loss of homeostasis in the environment of the progenitor cells of the sebaceous glands, for which the niche is located in the epithelium, close to the infundibulum, at the junction with the sebaceous duct. 11 A loss of homeostasis, which may be induced by comedogens (i.e., increased sebum free fatty acid [FFA] levels, C. acnes, local vitamin A deficiency, and dioxin-like xenobiotic factors), appears therefore to be involved in the early stages of development of typical acne lesions. 3,12,13,14,15 Maintaining homeostasis during the programmed differentiation of sebaceous stem cells in order to prevent microcomedone formation is a new goal in patients with acne-prone skin.…”

Section: Introductionmentioning

confidence: 99%

Tolerability and effectiveness of a dermocosmetic product containing Silybum marianum fruit extract in adolescents and young adults with acne‐prone skin: An international, phase IV, longitudinal study

Bageorgou

Beausillon³

et al. 2023

J of Cosmetic Dermatology

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Background Dermocosmetic products are often used to maintain or enhance the tolerance and effectiveness of medical anti‐acne therapies. Recent discoveries about the pathophysiology of acne‐prone skin indicate that skincare products may help maintain homeostasis around the sebaceous gland progenitor cells, thereby preventing microcomedone formation. Aims To evaluate the tolerance and effectiveness of a dermocosmetic product containing Silybum marianum fruit extract (SMFE) in adolescents and young adults with acne‐prone skin. Patients/Methods This real‐life, international, observational, multicenter study was conducted in patients aged 12–25 years with mild‐to‐moderate acne. Patients (N = 4230) used the product twice daily for 8–12 weeks, either alone before (“initial group”) or after an anti‐acne therapy (“maintenance group”), or in association with their usual prescribed anti‐acne therapies (“association group”). The tolerance, effectiveness, and cosmetic properties of the product were assessed. Patient quality of life (QoL) was also evaluated. Results Dermatologists rated the tolerance of the product as “good” or “very good” in about 95% of the patients and the effectiveness of the product as “effective” or “highly effective” in about 80% of the patients, with a significant reduction in the mean global evaluation of acne (GEA) grade (−36% ± 39%, p < 0.0001) at study end. The QoL of most patients (80%) improved by the end of the study, and the majority (79% to 94%) appreciated the cosmetic properties of the product. Overall, the product was a clinical success in >84% of patients. Conclusions This dermocosmetic product can be used by adolescents and young adults with acne‐prone skin to limit the initial or chronic use of medical anti‐acne therapies.

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Aberrant Wnt Signaling Induces Comedo-Like Changes in the Murine Upper Hair Follicle

Cited by 4 publications

References 68 publications

Genome-wide meta-analysis identifies novel loci conferring risk of acne vulgaris

Genome-wide meta-analysis identifies novel loci conferring risk of acne vulgaris

Aging in the sebaceous gland

Tolerability and effectiveness of a dermocosmetic product containing Silybum marianum fruit extract in adolescents and young adults with acne‐prone skin: An international, phase IV, longitudinal study

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