title: Reelin expression is up-regulated in mice colon in response to acute colitis and provides resistance against colitis.
abstract: Reelin is an extracellular matrix protein first known for its key role in neuronal migration. Studies in rodent small intestine suggested that reelin protects the organism from intestinal pathology. Here we determined in mice colon, by real time-PCR and immunological assays, the expression of the reelin signalling system; its response to dextran sulphate sodium (DSS) and the response of wild-type and reeler mice to DSS-treatment. DNA methylation was determined by bisulfite modification and sequencing of genomic DNA. In the colon mucosa reelin expression is restricted to the myofibroblasts, whereas both epithelial cells and myofibroblasts express reelin receptors (ApoER2 and VLDLR) and its effector protein Dab1. The muscle layer also expresses reelin. DSS-treatment reduces reelin expression in the muscle but it is activated in the mucosa. Activation of mucosal reelin is greater in magnitude and is delayed until after the activation of the myofibroblasts marker, α-SMA. This indicates that the DSS-induced reelin up-regulation results from changes in the reelin gene expression rather than from myofibroblasts proliferation. DSS-treatment does not modify Sp1 or Tbr1 mRNA abundance, but increases that of TGF-β1 and ApoER2, decreases that of CASK and DNMT1 and it also decreases the reelin promoter methylation. Finally, the reeler mice exhibit higher inflammatory scores than wild-type mice, indicating that the mutation increases the susceptibility to DSS-colitis. In summary, this data are the first to demonstrate that mouse distal colon increases reelin production in response to DSS-colitis via a DNMT1-dependent hypo-methylation of the gene promoter region and that reelin provides protection against colitis.
authors.affiliation: Departmento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, Spain.
authors.forename: Ana E
authors.initials: AE
authors.lastname: Carvajal
authors.affiliation: Departmento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, Spain.
authors.forename: María D
authors.initials: MD
authors.lastname: Vázquez-Carretero
authors.affiliation: Departmento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: García-Miranda
authors.affiliation: Departmento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, Spain.
authors.forename: María J
authors.initials: MJ
authors.lastname: Peral
authors.affiliation: Departmento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, Spain. Electronic address: calonge@us.es.
authors.forename: María L
authors.initials: ML
authors.lastname: Calonge
authors.affiliation: Departmento de Fisiología, Facultad de Farmacia, Universidad de Sevilla, Spain.
authors.forename: Anunciación A
authors.initials: AA
authors.lastname: Ilundain
mesh_terms: D000208:Acute Disease; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D003092:Colitis / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D000076123:DNA (Cytosine-5-)-Methyltransferase 1 / Q000235:genetics; D019175:DNA Methylation; D016264:Dextran Sulfate; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D008810:Mice, Inbred C57BL; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000235:genetics*; D015854:Up-Regulation
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; D016264:Dextran Sulfate; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; C000619381:Dnmt1 protein, mouse; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases
keywords: Colon; DNMT1; DSS-colitis; Reelin