Original ResearchFull Report: Basic and Translational—Alimentary TractIn Inflamed Intestinal Tissues and Epithelial Cells, Interleukin 22 Signaling Increases Expression of H19 Long Noncoding RNA, Which Promotes Mucosal Regeneration
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Materials and Methods
Detailed protocols are provided in the Supplementary Materials and Methods.
Inflammation Results in the Induction of Intestinal H19 Long Noncoding RNA That Is Localized to Lgr5+ and Lgr5– Epithelial Cells in the Intestinal Mucosa
Although lncRNAs are thought to be a vast family of functional molecules associated with diverse biological processes in cells, their roles in sustaining tissue homeostasis in vivo remain largely unknown. To fill this knowledge gap, we profiled gene expression in the small intestine of mice with lipopolysaccharide (LPS)-induced sepsis using RNA sequening (RNA-seq) transcriptome analysis. LPS challenge for 24 hours resulted in alterations in the expression of a large number of protein-coding
Discussion
H19 lncRNA is an imprinted and maternally expressed transcript that is found in various tissues during embryogenesis but is silenced after birth.17 Its expression can be reactivated in numerous disease conditions, such as tumors and rheumatoid arthritis.18, 19 H19-deficient mice appear healthy, develop normally, and are fertile,20 suggesting that H19 lncRNA is not essential for embryonic development and viability. However, little is known about the role of H19 lncRNA in inflammation and
Acknowledgments
The authors thank members of the Jun Sun laboratory for advice on preparing mouse intestinal epithelial organoids. Accession number for RNA-sequencing data in the Gene Expression Omnibus database: GSE97371. Author contributions: Study concept and design: H.G. and X.-D.T. were involved in the overall design of experiments and interpretation of results. H.G., H.-F.B., and F.L. performed in vivo experiments. H.G., H.-F.B., F.L., P.W., and X.W. performed in vitro experiments. H.G. and L.W. designed
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Conflicts of interest The authors disclose no conflicts.
Funding This study was supported in part by National Institute of Diabetes and Digestive and Kidney Diseases grant R01DK064240 (X.-D.T), National Institute of General Medical Sciences grants R01GM117628 (X.-D.T.) and R01GM122406 (X.-D.T.), US Department of Veterans Affairs Merit Award I01BX001690 (X.-D.T.), Dorothy M. and Edward E. Burwell Professorship (X.-D.T.), and Ministry of Health of the People’s Republic of China Special Project grant no. 201002020 (J.Q.). The sponsors had no role in study design or collection, analysis, or interpretation of the data.
Author names in bold designate shared co-first authorship.