PMID- 34090862 OWN - NLM STAT- MEDLINE DCOM- 20211011 LR - 20211011 IS - 1090-2422 (Electronic) IS - 0014-4827 (Linking) VI - 405 IP - 2 DP - 2021 Aug 15 TI - Ferredoxin reductase regulates proliferation, differentiation, cell cycle and lipogenesis but not apoptosis in SZ95 sebocytes. PG - 112680 LID - S0014-4827(21)00212-3 [pii] LID - 10.1016/j.yexcr.2021.112680 [doi] AB - Ferredoxin reductase (FDXR), a mitochondrial membrane-associated flavoprotein, is essential for electron transfer and modulates p53-dependent apoptosis in cancer cells.FDXR may be implicated in epidermal and sebocytic differentiation, but its explicit function in sebocytes remains to be elucidated. In the present study, immunohistochemistry revealed that FDXR expression was increased in sebaceous cells of acne lesions. FDXR, PPARgamma, LXRalpha/beta, SREBP1 and Sox9 expression was incremental during sebocyte differentiation. FDXR overexpression induced by Ad-GFP-FDXR infection enhanced differentiation, reactive oxygen species (ROS), lipogenesis and PPARgamma expression, and consequnently inhibited proliferation in SZ95 sebocytes. Flow cytometry showed that FDXR overexpression induced significant blockade of G2/M phase but had no effect on sub-G1 (apoptotic) sebocytes. Insulin-like growth factor-1 (IGF-1)-induced FDXR and PPARgamma expression and lipogenesis were abolished by pretreatment with PI3K inhibitor LY294002. These results suggest that FDXR overexpression might promote differentiation and lipogenesis via ROS production and suppress proliferation via G2/S blockade in SZ95 sebocytes. IGF-1 could facilitate differentiation and lipogenesis through PI3K/Akt/FDXR pathway. FDXR could serve as a potential marker of advanced sebaceous differentiation, and its overexpression may be involved in the development of acne lesions. CI - Copyright (c) 2021. Published by Elsevier Inc. FAU - Li, Meng-Tong AU - Li MT AD - Department of Dermatology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China. FAU - Pi, Xiao-Xue AU - Pi XX AD - Department of Dermatology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China. FAU - Cai, Xiao-Lin AU - Cai XL AD - Department of Dermatology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China. FAU - Liu, Si AU - Liu S AD - Department of Dermatology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China. FAU - Huang, Zheng AU - Huang Z AD - Department of Dermatology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China. FAU - Zouboulis, Christos C AU - Zouboulis CC AD - Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Center, Brandenburg Medical School Theodor Fontane, Dessau, Germany. FAU - Fan, Yi-Ming AU - Fan YM AD - Department of Dermatology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China. Electronic address: ymfan1963@163.com. FAU - Shi, Ge AU - Shi G AD - Department of Dermatology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China; Medical Cosmetic and Plastic Surgery Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China. Electronic address: shig9@mail.sysu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210604 PL - United States TA - Exp Cell Res JT - Experimental cell research JID - 0373226 RN - 0 (Ferredoxins) SB - IM MH - Apoptosis/*drug effects MH - Cell Cycle/*drug effects MH - Cell Differentiation/*drug effects MH - Cell Respiration/drug effects MH - Epithelial Cells/drug effects MH - Ferredoxins/*pharmacology MH - Humans MH - Lipogenesis/*drug effects OTO - NOTNLM OT - Differentiation OT - Ferredoxin reductase OT - Insulin-like growth factor 1 OT - Lipogenesis OT - Reactive oxygen species OT - Sebocytes EDAT- 2021/06/07 06:00 MHDA- 2021/10/12 06:00 CRDT- 2021/06/06 20:45 PHST- 2020/10/24 00:00 [received] PHST- 2021/05/07 00:00 [revised] PHST- 2021/05/28 00:00 [accepted] PHST- 2021/06/07 06:00 [pubmed] PHST- 2021/10/12 06:00 [medline] PHST- 2021/06/06 20:45 [entrez] AID - S0014-4827(21)00212-3 [pii] AID - 10.1016/j.yexcr.2021.112680 [doi] PST - ppublish SO - Exp Cell Res. 2021 Aug 15;405(2):112680. doi: 10.1016/j.yexcr.2021.112680. Epub 2021 Jun 4.