R W Clayton1,2, K Göbel1,3, C M Niessen3, R Paus2,4, M A M van Steensel1,5, X Lim1,5. 1. Skin Research Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore. 2. Centre for Dermatology Research, University of Manchester, and NIHR Manchester Biomedical Research Centre, Manchester, U.K. 3. Department of Dermatology, Cologne Excellence Cluster on Stress Responses in Aging Associated Diseases (CECAD), and Centre for Molecular Medicine Cologne, The University of Cologne, Germany. 4. Department of Dermatology and Cutaneous Surgery, University of Miami, Miller School of Medicine, Miami, FL, U.S.A. 5. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
Abstract
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.
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.
Authors: Shymaa Ahmed Maher; Nader Ali Ismail; Eman A Toraih; Alaa H Habib; Nawal S Gouda; Amal H A Gomaa; Manal S Fawzy; Ghada M Helal Journal: Biomolecules Date: 2022-04-19
Authors: Bénédicte Oulès; Christina Philippeos; Joe Segal; Matthieu Tihy; Matteo Vietri Rudan; Ana-Maria Cujba; Philippe A Grange; Sven Quist; Ken Natsuga; Lydia Deschamps; Nicolas Dupin; Giacomo Donati; Fiona M Watt Journal: Nat Commun Date: 2020-10-20 Impact factor: 14.919