Short communication: Glucagon-like peptide-2 and coccidiosis alter tight junction gene expression in the gastrointestinal tract of dairy calves

• Published in: Journal of dairy science Vol. 98; no. 5; pp. 3432 - 3437
• Main Authors: Walker, M P, Evock-Clover, C M, Elsasser, T H, Connor, E E
• Format: Journal Article
• Language: English
• Published: United States 01.05.2015
• Subjects: Animals; Animals, Newborn; Cattle; Cattle Diseases - drug therapy; Cattle Diseases - parasitology; Claudin-1 - genetics; Claudin-1 - metabolism; Claudin-2 - genetics; Claudin-2 - metabolism; Claudin-4 - genetics; Claudin-4 - metabolism; Coccidiosis - drug therapy; Coccidiosis - veterinary; Coxsackie and Adenovirus Receptor-Like Membrane Protein - genetics; Coxsackie and Adenovirus Receptor-Like Membrane Protein - metabolism; Eimeria - drug effects; Eimeria - isolation & purification; Gastrointestinal Tract - drug effects; Gastrointestinal Tract - parasitology; Gene Expression; Glucagon-Like Peptide 2 - pharmacology; Intestines - metabolism; Junctional Adhesion Molecule A - genetics; Junctional Adhesion Molecule A - metabolism; Occludin - genetics; Occludin - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Zonula Occludens-1 Protein - genetics; Zonula Occludens-1 Protein - metabolism; coccidiosis; tight junction protein; dairy calf; gene expression
• ISSN: 0022-0302; 1525-3198
• DOI: 10.3168/jds.2014-8919

Tight junction (TJ) proteins are integral factors involved in gut barrier function, and therapy with glucagon-like peptide-2 (GLP-2) enhances gut integrity. Our aim was to assess effects of GLP-2 treatment on mRNA expression of 8 TJ complex proteins in the intestine of dairy calves not infected or infected with Eimeria bovis at 11±3d of age. Mucosal epithelium from jejunum, ileum, and cecum was collected at slaughter from Holstein bull calves assigned to 4 groups: noninfected, buffer-treated (n=5); noninfected, GLP-2 treated (n=4); E. bovis-infected, buffer-treated (n=5); and E. bovis-infected, GLP-2-treated (n=4). Infected calves were orally dosed with 100,000 to 200,000 sporulated E. bovis oocysts on d 0; GLP-2-treated calves received 50 µg of GLP-2/kg of body weight subcutaneously twice daily for 10d beginning on d 18; and buffer-treated calves received an equal injection volume of 0.01 M Na bicarbonate buffer. All calves were killed on d 28. The mRNA expression of coxsackie and adenovirus receptor (CXADR), claudins 1, 2, and 4 (CLDN1, CLDN2, and CLDN4), F11 receptor (F11R), junction adhesion molecule 2 (JAM2), occludin (OCLN), and tight junction protein ZO-1 (TJP1) was determined by real-time quantitative PCR. In jejunum and ileum, an interaction of E. bovis infection and GLP-2 treatment on gene expression was noted. In jejunum of noninfected calves, GLP-2 increased CXADR, CLDN2, OCLN, and TJP1 mRNA expression but had no effect on mRNA expression in infected calves. Treatment with GLP-2 also increased tight junction protein ZO-1 protein expression in jejunum of noninfected calves as determined by immunohistochemistry. In ileum, E. bovis decreased expression of JAM2, OCLN, and TJP1 in buffer-treated calves, and GLP-2 increased TJP1 expression in infected calves. In cecum, E. bovis infection reduced expression of CXADR, CLDN4, F11R, and OCLN, and GLP-2 therapy increased expression of CLDN4, F11R, OCLN, and TJP1. Results are consistent with studies in nonruminants showing decreased expression of TJ complex proteins in the intestinal tract during pathogen-induced diarrhea and increased TJ protein expression in intestinal tissues in response to GLP-2 treatment. In conclusion, E. bovis reduces gene expression of TJ proteins primarily in cecum of calves 28d postinfection, and GLP-2 increases expression of selected TJ genes in intestinal tissues. Use of GLP-2 to improve gut barrier function in ruminants during pathogen-induced diarrhea warrants additional study.