Artículo
Reelin expression is up-regulated in mice colon in response to acute colitis and provides resistance against colitis
Autor/es | Carvajal Vázquez, Ana Eloisa
Vázquez Carretero, María Dolores García Miranda, Pablo Peral Rubio, María José Calonge Castrillo, María Luisa Ilundáin Larrañeta, María Anunciación Ana |
Fecha de publicación | 2017 |
Fecha de depósito | 2019-04-08 |
Publicado en |
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Resumen | 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 ... 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 |
Identificador del proyecto | CTS 5884 |
Cita | Carvajal Vázquez, A.E., Vázquez Carretero, M.D., García Miranda, P., Peral Rubio, M.J., Calonge Castrillo, M.L. y Ilundáin Larrañeta, M.A.A. (2017). Reelin expression is up-regulated in mice colon in response to acute colitis and provides resistance against colitis. Biochimica et Biophysica Acta Molecular and Cell Biology of Lipids, 1863 (2), 462-473. |
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Reelina inflamma para iDUS.pdf | 951.3Kb | [PDF] | Ver/ | Versión aceptada |