KeunOh Choi1, Mirim Jin2,3, Christos C Zouboulis4, YoungJoo Lee5. 1. Department of Bioscience and Biotechnology, Sejong University, Seoul, Republic of Korea. 2. Department of Microbiology, College of Medicine, Gachon University, Incheon, Republic of Korea. 3. Department of Health Science and Technology, GAHIST, Gachon University, Incheon, Republic of Korea. 4. Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane, Dessau, Germany. 5. Department of Bioscience and Biotechnology, Sejong University, Seoul, Republic of Korea, yjlee@sejong.ac.kr.
Abstract
BACKGROUND: Excessive sebum is produced by specialized cells called sebocytes and is considered a cause or consequence of acne, sebaceous cysts, hyperplasia, and sebaceous adenoma. OBJECTIVE: To report changes in lipid accumulation in human sebocytes under hypoxia, which occurs under conditions of seborrhea. METHODS: Sebocytes from the immortalized human gland cell line SZ95 were cultured under conditions of hypoxia for 48 h; lipid formation was confirmed by Nile red and Oil Red O staining. To investigate whether HIF-1α plays a role in lipid accumulation, SZ95 cells transfected or treated with dimethyloxalylglycine (DMOG) were assessed by Nile red. For protein expression of the sterol regulatory element-binding protein-1 (SREBP-1) and perilipin 2 (PLIN2), Western blot analysis was performed. Differentially expressed genes (DEGs) in SZ95 sebocytes under hypoxia were revealed by RNA-Seq analyses, and the statistical significance of the correlation between hypoxic and acne/non-acne skin was evaluated using gene set enrichment analysis. RESULTS: Hypoxia induces lipid accumulation in SZ95 sebocytes. In addition, the levels of SREBP-1 and PLIN2 were regulated by HIF-1α in SZ95 sebocytes under hypoxia. RNA-Seq analyses of DEGs in SZ95 sebocytes under hypoxia revealed 256 DEGs, including several lipid droplet-associated genes. DEGs between acne and non-acne skin are significantly enriched in hypoxia gene sets. We also detected 93 differentially expressed inflammatory mediators. CONCLUSIONS: To the best of our knowledge, this study is the first to show that a hypoxic microenvironment can increase lipogenesis and provides a link between seborrhea and inflammation.
BACKGROUND: Excessive sebum is produced by specialized cells called sebocytes and is considered a cause or consequence of acne, sebaceous cysts, hyperplasia, and sebaceous adenoma. OBJECTIVE: To report changes in lipid accumulation in human sebocytes under hypoxia, which occurs under conditions of seborrhea. METHODS: Sebocytes from the immortalized human gland cell line SZ95 were cultured under conditions of hypoxia for 48 h; lipid formation was confirmed by Nile red and Oil Red O staining. To investigate whether HIF-1α plays a role in lipid accumulation, SZ95 cells transfected or treated with dimethyloxalylglycine (DMOG) were assessed by Nile red. For protein expression of the sterol regulatory element-binding protein-1 (SREBP-1) and perilipin 2 (PLIN2), Western blot analysis was performed. Differentially expressed genes (DEGs) in SZ95 sebocytes under hypoxia were revealed by RNA-Seq analyses, and the statistical significance of the correlation between hypoxic and acne/non-acne skin was evaluated using gene set enrichment analysis. RESULTS:Hypoxia induces lipid accumulation in SZ95 sebocytes. In addition, the levels of SREBP-1 and PLIN2 were regulated by HIF-1α in SZ95 sebocytes under hypoxia. RNA-Seq analyses of DEGs in SZ95 sebocytes under hypoxia revealed 256 DEGs, including several lipid droplet-associated genes. DEGs between acne and non-acne skin are significantly enriched in hypoxia gene sets. We also detected 93 differentially expressed inflammatory mediators. CONCLUSIONS: To the best of our knowledge, this study is the first to show that a hypoxic microenvironment can increase lipogenesis and provides a link between seborrhea and inflammation.
Authors: Jian Jin; Banrida Wahlang; Monika Thapa; Kimberly Z Head; Josiah E Hardesty; Sudhir Srivastava; Michael L Merchant; Shesh N Rai; Russell A Prough; Matthew C Cave Journal: Acta Pharm Sin B Date: 2021-10-21 Impact factor: 14.903