Development and resolution of experimental colitis in mice with targeted deletion of dipeptidyl peptidase IV.
Glucagon-like peptide-2 (GLP-2) is a potent intestinotrophic growth factor that enhances repair of damaged intestinal tissue. However, its bioactivity is limited by dipeptidyl peptidase IV (DPIV)-mediated degradation. We hypothesized that DPIV(-/-) mice would display an increased resistance to, and an enhanced recovery from, dextran sulfate sodium (DSS)-induced colitis compared to DPIV(+/+) mice. DPIV(+/+) and DPIV(-/-) mice consumed 2% DSS for 6 days, followed by a 15 day recovery period. Mice were killed at days 0, 3, 6, 9, 14, and 21 (n = 6-8) and the small intestine and colon removed for histological assessment of villus height, crypt depth, and crypt area. The epithelial cell proliferative labeling index was determined by proliferating cell nuclear antigen (PCNA) immunostaining. Small intestine, colon, and total body weight did not differ between DPIV(+/+) and DPIV(-/-) mice. Distal colon crypt depth did not differ significantly between DPIV(+/+) and DPIV(-/-) mice during the development of DSS-colitis or during the recovery phase. Similarly no significant effects were apparent on distal colon crypt area or PCNA labeling index between DPIV(+/+) and DPIV(-/-) during the development of and recovery from DSS-colitis. However, DPIV(-/-) mice still possessed significant levels of plasma DPIV-like activity. We conclude that loss of DPIV activity does not increase resistance to experimental colitis and hypothesize that other DPIV family members may also be involved in the cleavage of GLP-2.
Geier
Mark S
MS
Child Health Research Institute and Centre for Paediatric and Adolescent Gastroenterology, Women's and Children's Hospital, North Adelaide, South Australia, Australia.
Tenikoff
Danik
D
Yazbeck
Roger
R
McCaughan
Geoffrey W
GW
Abbott
Catherine A
CA
Howarth
Gordon S
GS
D000818:Animals; D001835:Body Weight; D003092:Colitis / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D003106:Colon / Q000473:pathology; D016264:Dextran Sulfate; D018819:Dipeptidyl Peptidase 4 / Q000097:blood / Q000235:genetics*; D018450:Disease Progression; D017353:Gene Deletion; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009929:Organ Size; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism
D018809:Proliferating Cell Nuclear Antigen; D016264:Dextran Sulfate; D018819:Dipeptidyl Peptidase 4