phaidra.vetmeduni.ac.at o:3058 DOI 10.1371/journal.pone.0296024 Expression of the cobalamin transporters cubam and MRP1 in the canine ileum-Upregulation in chronic inflammatory enteropathy Chronic inflammatory enteropathy (CIE) in dogs, a spontaneous model of human inflammatory bowel disease (IBD), is associated with a high rate of cobalamin deficiency. The etiology of hypocobalaminemia in human IBD and canine CIE remains unknown, and compromised intestinal uptake of cobalamin resulting from ileal cobalamin receptor deficiency has been proposed as a possible cause. Here, we evaluated the intestinal expression of the cobalamin receptor subunits, amnionless (AMN) and cubilin (CUBN), and the basolateral efflux transporter multi-drug resistance protein 1 (MRP1) in 22 dogs with CIE in comparison to healthy dogs. Epithelial CUBN and AMN levels were quantified by confocal laser scanning microscopy using immunohistochemistry in endoscopic ileal biopsies from dogs with (i) CIE and normocobalaminemia, (ii) CIE and suboptimal serum cobalamin status, (iii) CIE and severe hypocobalaminemia, and (iv) healthy controls. CUBN and MRP1 expression was quantified by RT-qPCR. Receptor expression was evaluated for correlation with clinical patient data. Ileal mucosal protein levels of AMN and CUBN as well as mRNA levels of CUBN and MRP1 were significantly increased in dogs with CIE compared to healthy controls. Ileal cobalamin receptor expression was positively correlated with age, clinical disease activity index (CCECAI) score, and lacteal dilation in the ileum, inversely correlated with serum folate concentrations, but was not associated with serum cobalamin concentrations. Cobalamin receptor downregulation does not appear to be the primary cause of hypocobalaminemia in canine CIE. In dogs of older age with severe clinical signs and/or microscopic intestinal lesions, intestinal cobalamin receptor upregulation is proposed as a mechanism to compensate for CIE-associated hypocobalaminemia. These results support oral supplementation strategies in hypocobalaminemic CIE patients. eng Methylmalonic Acid Concentrations; Messenger-Rna Expression; Bowel-Disease; Gene-Expression; Gastrointestinal Inflammation; Laboratory Tests; Serum Cobalamin; Dogs; Vitamin-B12; Deficiency 2024-06-03T08:16:32.045Z LOMv1.0 Author BEGIN:VCARD VERSION:3.0 N:Kather;Stefanie; FN:Stefanie Kather X-ORCID:https://orcid.org/0000-0001-5519-9107 END:VCARD BEGIN:VCARD VERSION:3.0 N:Heilmann;Romy M.; FN:Romy M. Heilmann X-ORCID:https://orcid.org/0000-0003-3485-5157 END:VCARD BEGIN:VCARD VERSION:3.0 N:Dengler;Franziska; FN:Franziska Dengler X-ORCID:https://orcid.org/0000-0002-2178-2270 END:VCARD BEGIN:VCARD VERSION:3.0 N:Gäbel;Gotthold; FN:Gotthold Gäbel END:VCARD BEGIN:VCARD VERSION:3.0 N:Steiner;Joerg M.; FN:Joerg M. Steiner END:VCARD BEGIN:VCARD VERSION:3.0 N:Sung;Chi-Hsuan; FN:Chi-Hsuan Sung END:VCARD BEGIN:VCARD VERSION:3.0 N:Böttcher;Denny; FN:Denny Böttcher X-ORCID:https://orcid.org/0000-0001-8986-4873 END:VCARD BEGIN:VCARD VERSION:3.0 N:Kacza;Johannes; FN:Johannes Kacza END:VCARD BEGIN:VCARD VERSION:3.0 N:Pfannkuche;Helga; FN:Helga Pfannkuche END:VCARD https://w3id.org/kim/hcrt/scheme https://w3id.org/kim/hcrt/text Textdokument Text LOMv1.0 yes https://creativecommons.org/licenses/by/4.0 application/pdf 630850 https://phaidra.vetmeduni.ac.at/o:3058 https://phaidra.vetmeduni.ac.at/api/object/o:3058/thumbnail LOMv1.0 discipline