title: Differential miRNA profile on photoaged primary human fibroblasts irradiated with ultraviolet A.
abstract: Photoaging is cell aging caused by long-wave ultraviolet (UVA) radiation which is the main cause of human skin aging produced by exogenous environment. As an endogenous noncoding small RNA, microRNAs (miRNAs) are sensitive to environmental changes, and the expression change of miRNAs is an important manner to adjust to environment. However, the miRNA profile on photoaged human skin irradiated with UVA remains unknown and whether UVA responsive miRNAs participate in the UVA-caused stress reaction of skin cells is also unclear. In this study, we established an in vitro photoaging model with UVA-radiated human primary cultured fibroblasts, which could mimic UVA-induced photoaging of skin. Differentially expressed miRNAs during photoaging, including five up- and seven downregulated miRNAs, were found by microarray analysis and were verified by quantitative real-time PCR. With bioinformatics methods, the predicted miRNA targets were suggested to be associated with pathways in cancers. Among the significantly UVA-downregulated miRNAs, miR-146a overexpression antagonized the UVA-induced proliferation inhibition and suppressed the upregulation of aging-related genes in photoaging of our model. Western blot and luciferase assay showed that Smad4 might be a target of miR-146a to exert miR-146a functions during photoaging. Therefore, UVA radiation-induced photoaging results in specific patterns of miRNA response and miR-146a are able to antagonize UVA-caused photoaging partially through targeting Smad4.
authors.affiliation: Department of Dermatology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Bing-Rong
authors.initials: BR
authors.lastname: Zhou
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Hua
authors.forename: Ze
authors.initials: Z
authors.lastname: Guo
authors.forename: Dan
authors.initials: D
authors.lastname: Luo
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D049109:Cell Proliferation / Q000528:radiation effects; D002478:Cells, Cultured; D015536:Down-Regulation / Q000528:radiation effects; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015595:Skin Aging / Q000235:genetics / Q000528:radiation effects; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome / Q000528:radiation effects*; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000528:radiation effects
chemical_list: D020413:3' Untranslated Regions; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D008156:Luciferases