Geier Mark S, Tenikoff Danik, Yazbeck Roger, McCaughan Geoffrey W, Abbott Catherine A, Howarth Gordon S
Child Health Research Institute and Centre for Paediatric and Adolescent Gastroenterology, Women's and Children's Hospital, North Adelaide, South Australia, Australia.
J Cell Physiol. 2005 Aug;204(2):687-92. doi: 10.1002/jcp.20333.
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.
胰高血糖素样肽-2（GLP-2）是一种强效的肠营养生长因子，可增强受损肠组织的修复。然而，其生物活性受到二肽基肽酶IV（DPIV）介导的降解的限制。我们假设，与DPIV(+/+)小鼠相比，DPIV(-/-)小鼠对葡聚糖硫酸钠（DSS）诱导的结肠炎具有更高的抵抗力，并且恢复得更快。DPIV(+/+)和DPIV(-/-)小鼠饮用2%的DSS溶液6天，随后进入15天的恢复期。在第0、3、6、9、14和21天处死小鼠（n = 6-8），取出小肠和结肠，进行组织学评估，测量绒毛高度、隐窝深度和隐窝面积。通过增殖细胞核抗原（PCNA）免疫染色来确定上皮细胞增殖标记指数。DPIV(+/+)和DPIV(-/-)小鼠的小肠、结肠和总体重没有差异。在DSS诱导的结肠炎发展过程或恢复阶段，DPIV(+/+)和DPIV(-/-)小鼠的远端结肠隐窝深度没有显著差异。同样，在DSS诱导的结肠炎发展和恢复过程中，DPIV(+/+)和DPIV(-/-)小鼠的远端结肠隐窝面积或PCNA标记指数也没有明显的显著影响。然而，DPIV(-/-)小鼠的血浆中仍具有显著水平的DPIV样活性。我们得出结论，DPIV活性的丧失并不会增加对实验性结肠炎的抵抗力，并推测其他DPIV家族成员可能也参与了GLP-2的裂解。
