| http://purl.uniprot.org/citations/26752649 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26752649 | http://www.w3.org/2000/01/rdf-schema#comment | "Although defects in intestinal barrier function are a key pathogenic factor in patients with inflammatory bowel diseases (IBDs), the molecular pathways driving disease-specific alterations of intestinal epithelial cells (IECs) are largely unknown. Here, we addressed this issue by characterizing the transcriptome of IECs from IBD patients using a genome-wide approach. We observed disease-specific alterations in IECs with markedly impaired Rho-A signaling in active IBD patients. Localization of epithelial Rho-A was shifted to the cytosol in IBDs, and inflammation was associated with suppressed Rho-A activation due to reduced expression of the Rho-A prenylation enzyme geranylgeranyltransferase-I (GGTase-I). Functionally, we found that mice with conditional loss of Rhoa or the gene encoding GGTase-I, Pggt1b, in IECs exhibit spontaneous chronic intestinal inflammation with accumulation of granulocytes and CD4+ T cells. This phenotype was associated with cytoskeleton rearrangement and aberrant cell shedding, ultimately leading to loss of epithelial integrity and subsequent inflammation. These findings uncover deficient prenylation of Rho-A as a key player in the pathogenesis of IBDs. As therapeutic triggering of Rho-A signaling suppressed intestinal inflammation in mice with GGTase-I-deficient IECs, our findings suggest new avenues for treatment of epithelial injury and mucosal inflammation in IBD patients."xsd:string |
| http://purl.uniprot.org/citations/26752649 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci80997"xsd:string |
| http://purl.uniprot.org/citations/26752649 | http://purl.uniprot.org/core/author | "Becker C."xsd:string |
| http://purl.uniprot.org/citations/26752649 | http://purl.uniprot.org/core/author | "Watson A.J."xsd:string |
| http://purl.uniprot.org/citations/26752649 | http://purl.uniprot.org/core/author | "Amann K."xsd:string |
| http://purl.uniprot.org/citations/26752649 | http://purl.uniprot.org/core/author | "Brakebusch C."xsd:string |
| http://purl.uniprot.org/citations/26752649 | http://purl.uniprot.org/core/author | "Ekici A.B."xsd:string |
| http://purl.uniprot.org/citations/26752649 | http://purl.uniprot.org/core/author | "Tenzer S."xsd:string |
| http://purl.uniprot.org/citations/26752649 | http://purl.uniprot.org/core/author | "Gunther C."xsd:string |
| http://purl.uniprot.org/citations/26752649 | http://purl.uniprot.org/core/author | "Neurath M.F."xsd:string |
| http://purl.uniprot.org/citations/26752649 | http://purl.uniprot.org/core/author | "Atreya I."xsd:string |
| http://purl.uniprot.org/citations/26752649 | http://purl.uniprot.org/core/author | "Wirtz S."xsd:string |
| http://purl.uniprot.org/citations/26752649 | http://purl.uniprot.org/core/author | "Atreya R."xsd:string |
| http://purl.uniprot.org/citations/26752649 | http://purl.uniprot.org/core/author | "Danese S."xsd:string |
| http://purl.uniprot.org/citations/26752649 | http://purl.uniprot.org/core/author | "Bergo M."xsd:string |
| http://purl.uniprot.org/citations/26752649 | http://purl.uniprot.org/core/author | "Vetrano S."xsd:string |
| http://purl.uniprot.org/citations/26752649 | http://purl.uniprot.org/core/author | "Lopez-Posadas R."xsd:string |
| http://purl.uniprot.org/citations/26752649 | http://purl.uniprot.org/core/author | "Fiorino G."xsd:string |
| http://purl.uniprot.org/citations/26752649 | http://purl.uniprot.org/core/author | "Billmeier U."xsd:string |
| http://purl.uniprot.org/citations/26752649 | http://purl.uniprot.org/core/author | "Thonn V."xsd:string |
| http://purl.uniprot.org/citations/26752649 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |
| http://purl.uniprot.org/citations/26752649 | http://purl.uniprot.org/core/name | "J Clin Invest"xsd:string |
| http://purl.uniprot.org/citations/26752649 | http://purl.uniprot.org/core/pages | "611-626"xsd:string |
| http://purl.uniprot.org/citations/26752649 | http://purl.uniprot.org/core/title | "Rho-A prenylation and signaling link epithelial homeostasis to intestinal inflammation."xsd:string |