title: Analysis of the microRNA expression profile of normal human dermal papilla cells treated with 5α-dihydrotestosterone.
abstract: Clinical evidence has demonstrated that the accumulation of 5α-dihydrotestosterone (DHT) in dermal papilla cells (DPCs) is implicated in androgenetic alopecia. Whether this accumulation in DHT may have direct cellular effects leading to androgenetic alopecia remains to be elucidated. The present study aimed to determine whether DHT affects cell growth, cell cycle arrest, cell death, senescence and the induction of reactive oxygen species (ROS), and whether these effects are mediated by microRNA (miRNA)-dependent mechanisms. The cell viability and cell cycle were determined, levels of ROS were examined and senescence-associated β-galactosidase assays were performed in normal human DPCs (nHDPCs). Furthermore, miRNA expression profiling was performed using an miRNA microarray to determine whether changes in the expression levels of miRNA were associated with the cellular effects of DHT. The results revealed that DHT decreased cell growth by inducing cell death and G2 cell cycle arrest, and by increasing the production of ROS and senescence in the nHDPCs. In addition, 55 miRNAs were upregulated and 6 miRNAs were downregulated in the DHT-treated nHDPCs. Bioinformatic analysis demonstrated that the putative target genes of these upregulated and downregulated miRNAs were involved in cell growth, cell cycle arrest, cell death, senescence and the production of ROS. Specifically, the target genes of five highly upregulated and downregulated miRNAs were identified and were associated with the aforementioned effects of DHT. These results demonstrated that the expression of miRNA was altered in the DHT-treated nHDPCs and suggest the potential mechanisms of DHT-induced cell growth repression, cell cycle arrest, cell death, senescence and induction of ROS.
authors.affiliation: Korea Institute for Skin and Clinical Sciences and Molecular‑Targeted Drug Research Center, Konkuk University, Seoul 143‑701, Republic of Korea.
authors.forename: Myung Joo
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Korea Institute for Skin and Clinical Sciences and Molecular‑Targeted Drug Research Center, Konkuk University, Seoul 143‑701, Republic of Korea.
authors.forename: Hwa Jun
authors.initials: HJ
authors.lastname: Cha
authors.affiliation: Korea Institute for Skin and Clinical Sciences and Molecular‑Targeted Drug Research Center, Konkuk University, Seoul 143‑701, Republic of Korea.
authors.forename: Kyung Mi
authors.initials: KM
authors.lastname: Lim
authors.affiliation: Korea Institute for Skin and Clinical Sciences and Molecular‑Targeted Drug Research Center, Konkuk University, Seoul 143‑701, Republic of Korea.
authors.forename: Ok-Kyu
authors.initials: OK
authors.lastname: Lee
authors.affiliation: Korea Institute for Skin and Clinical Sciences and Molecular‑Targeted Drug Research Center, Konkuk University, Seoul 143‑701, Republic of Korea.
authors.forename: Seunghee
authors.initials: S
authors.lastname: Bae
authors.affiliation: Korea Institute of Radiological and Medical Sciences, Seoul 139‑706, Republic of Korea.
authors.forename: Chun-Ho
authors.initials: CH
authors.lastname: Kim
authors.affiliation: Korea Institute of Radiological and Medical Sciences, Seoul 139‑706, Republic of Korea.
authors.forename: Kee-Ho
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Dermatology, Konkuk University School of Medicine, Seoul 143‑729, Republic of Korea.
authors.forename: Yu Na
authors.initials: YN
authors.lastname: Lee
authors.affiliation: Department of Dermatology, Konkuk University School of Medicine, Seoul 143‑729, Republic of Korea.
authors.forename: Kyu Joong
authors.initials: KJ
authors.lastname: Ahn
authors.affiliation: Korea Institute for Skin and Clinical Sciences and Molecular‑Targeted Drug Research Center, Konkuk University, Seoul 143‑701, Republic of Korea.
authors.forename: Sungkwan
authors.initials: S
authors.lastname: An
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects; D020405:Dermis / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013196:Dihydrotestosterone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D017930:Genes, Reporter; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism; D015398:Signal Transduction; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D017382:Reactive Oxygen Species; D013196:Dihydrotestosterone; D001616:beta-Galactosidase