title: MiR-375 is downregulated in epithelial cells after IL-13 stimulation and regulates an IL-13-induced epithelial transcriptome.
abstract: Interleukin 13 (IL-13)-induced epithelial gene and protein expression changes are central to the pathogenesis of multiple allergic diseases. Herein, using human esophageal squamous and bronchial columnar epithelial cells, we identified microRNAs (miRNAs) that were differentially regulated after IL-13 stimulation. Among the IL-13-regulated miRNAs, miR-375 showed a conserved pattern of downregulation. Furthermore, miR-375 was downregulated in the lung of IL-13 lung transgenic mice. We subsequently analyzed miR-375 levels in a human disease characterized by IL-13 overproduction--the allergic disorder eosinophilic esophagitis (EE)--and observed downregulation of miR-375 in EE patient samples compared with control patients. MiR-375 expression levels reflected disease activity, normalized with remission, and inversely correlated with the degree of allergic inflammation. Using a lentiviral strategy and whole-transcriptome analysis in epithelial cells, miR-375 overexpression was sufficient to markedly modify IL-13-associated immunoinflammatory pathways in epithelial cells in vitro, further substantiating interactions between miR-375 and IL-13. Taken together, our results support a key role of miRNAs, particularly miR-375, in regulating and fine-tuning IL-13-mediated responses.
authors.affiliation: Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
authors.forename: T X
authors.initials: TX
authors.lastname: Lu
authors.forename: E-J
authors.initials: EJ
authors.lastname: Lim
authors.forename: T
authors.initials: T
authors.lastname: Wen
authors.forename: A J
authors.initials: AJ
authors.lastname: Plassard
authors.forename: S P
authors.initials: SP
authors.lastname: Hogan
authors.forename: L J
authors.initials: LJ
authors.lastname: Martin
authors.forename: B J
authors.initials: BJ
authors.lastname: Aronow
authors.forename: M E
authors.initials: ME
authors.lastname: Rothenberg
mesh_terms: D000818:Animals; D002460:Cell Line; D016000:Cluster Analysis; D057765:Eosinophilic Esophagitis / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D004947:Esophagus / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D018793:Interleukin-13 / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism; D059467:Transcriptome
chemical_list: D007155:Immunologic Factors; D018793:Interleukin-13; D035683:MicroRNAs