title: MicroRNA-143 inhibits IL-13-induced dysregulation of the epidermal barrier-related proteins in skin keratinocytes via targeting to IL-13Rα1.
abstract: Atopic dermatitis is a chronic inflammatory skin disease characterized by the dysregulation of the epidermal barrier and the immune system. Interleukin (IL)-13, a key T helper 2 cytokine, has been shown to impair the epidermal barrier function via downregulating epidermal barrier proteins. MicroRNAs are small noncoding RNAs of approximately 22 nucleotides that act as negative regulators of gene expression at posttranscriptional levels. MicroRNA-143 is known to be a tumor suppressor in various tumors; however, its role in the regulation of allergic diseases including atopic dermatitis remains elusive. In this study, we investigated whether IL-13Rα1 was a microRNA-143 target to regulate the effects of IL-13 on epidermal barrier function. After the stimulation of IL-13 in human epidermal keratinocytes, the level of microRNA-143 was decreased. The luciferase activity of the vector containing 3'UTR of IL-13Rα1 was decreased in keratinocytes transfected with microRNA-143 mimic compared to those of the corresponding controls. The forced expression of microRNA-143 mimic blocked the IL-13-induced downregulation of filaggrin, loricrin, and involucrin in epidermal keratinocytes. Collectively, these data suggest that microRNA-143 suppresses IL-13 activity and inflammation through targeting of IL-13Rα1 in epidermal keratinocytes. MicroRNA-143 may serve as a potential preventive and therapeutic target in atopic dermatitis.
authors.affiliation: Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Yue-Ping
authors.initials: YP
authors.lastname: Zeng
authors.affiliation: Department of Dermatology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Giang Huong
authors.initials: GH
authors.lastname: Nguyen
authors.affiliation: Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. jinhongzhong@263.net.
authors.forename: Hong-Zhong
authors.initials: HZ
authors.lastname: Jin
mesh_terms: D002478:Cells, Cultured; D003876:Dermatitis, Atopic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004817:Epidermis / Q000378:metabolism* / Q000473:pathology; D000091344:Filaggrin Proteins; D006801:Humans; D018793:Interleukin-13 / Q000096:biosynthesis* / Q000235:genetics; D053661:Interleukin-13 Receptor alpha1 Subunit / Q000096:biosynthesis* / Q000235:genetics; D007381:Intermediate Filament Proteins / Q000096:biosynthesis / Q000235:genetics; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; C578095:IL13 protein, human; C508181:IL13RA1 protein, human; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D007381:Intermediate Filament Proteins; C542359:MIRN143 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D011498:Protein Precursors; C064554:loricrin; C032253:involucrin
keywords: Atopic dermatitis; Filaggrin; Interleukin-13; Involucrin; Loricrin; MicroRNA-143