title: HuR Enhances Early Restitution of the Intestinal Epithelium by Increasing Cdc42 Translation.
abstract: The mammalian intestinal mucosa exhibits a spectrum of responses after acute injury and repairs itself rapidly to restore the epithelial integrity. The RNA-binding protein HuR regulates the stability and translation of target mRNAs and is involved in many aspects of gut epithelium homeostasis, but its exact role in the regulation of mucosal repair after injury remains unknown. We show here that HuR is essential for early intestinal epithelial restitution by increasing the expression of cell division control protein 42 (Cdc42) at the posttranscriptional level. HuR bound to theCdc42mRNA via its 3' untranslated region, and this association specifically enhanced Cdc42 translation without an effect on theCdc42mRNA level. Intestinal epithelium-specific HuR knockout not only decreased Cdc42 levels in mucosal tissues, but it also inhibited repair of damaged mucosa induced by mesenteric ischemia/reperfusion in the small intestine and by dextran sulfate sodium in the colon. Furthermore, Cdc42 silencing prevented HuR-mediated stimulation of cell migration over the wounded area by altering the subcellular distribution of F-actin. These results indicate that HuR promotes early intestinal mucosal repair after injury by increasing Cdc42 translation and demonstrate the importance of HuR deficiency in the pathogenesis of delayed mucosal healing in certain pathological conditions.
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.|Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA.
authors.forename: Lan
authors.initials: L
authors.lastname: Liu
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.|Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA.
authors.forename: Ran
authors.initials: R
authors.lastname: Zhuang
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.|Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA.
authors.forename: Lan
authors.initials: L
authors.lastname: Xiao
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.|Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA.
authors.forename: Hee Kyoung
authors.initials: HK
authors.lastname: Chung
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.|Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Luo
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.|Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Turner
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.|Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA.
authors.forename: Jaladanki N
authors.initials: JN
authors.lastname: Rao
authors.affiliation: Laboratory of Genetics and Genomics, National Institute on Aging-IRP, National Institutes of Health, Baltimore, Maryland, USA.
authors.forename: Myriam
authors.initials: M
authors.lastname: Gorospe
authors.affiliation: Cell Biology Group, Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA jywang@som.umaryland.edu.|Baltimore Veterans Affairs Medical Center, Baltimore, Maryland, USA.|Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D002465:Cell Movement; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate; D000067780:ELAV-Like Protein 1 / Q000378:metabolism*; D020895:Enterocytes / Q000378:metabolism; D017353:Gene Deletion; D020868:Gene Silencing; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D007421:Intestine, Small / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014945:Wound Healing; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D020413:3' Untranslated Regions; D000067780:ELAV-Like Protein 1; D012333:RNA, Messenger; D016264:Dextran Sulfate; D020764:cdc42 GTP-Binding Protein
keywords: cell migration; gut epithelial restitution; mRNA stability; mucosal homeostasis; small GTPases; translation