Short communication: Glucagon-like peptide-2 and coccidiosis alter tight junction gene expression in the gastrointestinal tract of dairy calves.
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.
USDA, Agricultural Research Service, Animal Genomics and Improvement Laboratory, Beltsville, MD 20705.
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MP
Walker
USDA, Agricultural Research Service, Animal Genomics and Improvement Laboratory, Beltsville, MD 20705.
C M
CM
Evock-Clover
USDA, Agricultural Research Service, Animal Genomics and Improvement Laboratory, Beltsville, MD 20705.
T H
TH
Elsasser
USDA, Agricultural Research Service, Animal Genomics and Improvement Laboratory, Beltsville, MD 20705. Electronic address: erin.connor@ars.usda.gov.
E E
EE
Connor
D000818:Animals; D000831:Animals, Newborn; D002417:Cattle; D002418:Cattle Diseases / Q000188:drug therapy / Q000469:parasitology; D062445:Claudin-1 / Q000235:genetics / Q000378:metabolism; D062446:Claudin-2 / Q000235:genetics / Q000378:metabolism; D062506:Claudin-4 / Q000235:genetics / Q000378:metabolism; D003048:Coccidiosis / Q000188:drug therapy* / Q000662:veterinary; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein / Q000235:genetics / Q000378:metabolism; D004539:Eimeria / Q000187:drug effects / Q000302:isolation & purification; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000469:parasitology*; D015870:Gene Expression; D053767:Glucagon-Like Peptide 2 / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism; D062745:Junctional Adhesion Molecule A / Q000235:genetics / Q000378:metabolism; D062793:Occludin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000235:genetics* / Q000378:metabolism
D062445:Claudin-1; D062446:Claudin-2; D062506:Claudin-4; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D053767:Glucagon-Like Peptide 2; D062745:Junctional Adhesion Molecule A; D062793:Occludin; D012333:RNA, Messenger; D062826:Zonula Occludens-1 Protein
coccidiosis; dairy calf; gene expression; tight junction protein