TY - JOUR
T1 - Homeostasis of the sebaceous gland and mechanisms of acne pathogenesis
AU - Clayton, R. W.
AU - Göbel, K.
AU - Niessen, C. M.
AU - Paus, R.
AU - van Steensel, M. A.M.
AU - Lim, X.
N1 - Funding Information:
Funding sources R.W.C. is supported by a joint studentship between The University of Manchester and the A*STAR Research Attachment Programme (ARAP), Singapore. K.G. is also jointly supported by ARAP, Singapore, and The University of Cologne. M.A.M.vS. and X.L. are funded by the Biomedical Research Council, A*STAR Singapore, grants IAF-PP H17/01/a0/004 and IAF-PP H17/01/a0/008. C.M.N. is supported by DFG SFB 829 A5 and Z2, and German Cancer Aid. R.P. is supported by the NIHR Manchester Biomedical Research Centre, Inflammatory Hair Disease Programme. The authors wish to thank Dr Ivo J.H.M. de Vos for proofreading and assistance with design of the figures, and the Inkscape? team for the software used to generate Figures, and. The authors also wish to thank Professor Desmond Tobin for his help in acquiring the photomicrographs featured in Figure. The authors would also like to extend apologies to those whose works are relevant to this review, but which, due to space limitations, were not included within the main text.
Publisher Copyright:
© 2019 British Association of Dermatologists
PY - 2019/10/1
Y1 - 2019/10/1
N2 - 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.
AB - 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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U2 - 10.1111/bjd.17981
DO - 10.1111/bjd.17981
M3 - Review article
C2 - 31056753
AN - SCOPUS:85062779324
VL - 181
SP - 677
EP - 690
JO - British Journal of Dermatology
JF - British Journal of Dermatology
SN - 0007-0963
IS - 4
ER -