Glucagon-Like Peptide-2 Requires a Full Complement of Bmi-1 for Its Proliferative Effects in the Murine Small Intestine

摘要: The intestinal hormone, glucagon-like peptide-2 (GLP-2), stimulates growth, survival, and function of the epithelium through increased crypt cell proliferation, a long-acting analog has recently been approved to enhance capacity in patients with short bowel syndrome. goal present study was determine whether GLP-2-induced proliferation requires full complement B-cell lymphoma Moloney murine leukemia virus insertion region-1 homolog (Bmi-1), using Bmi-1(eGFP/+) mouse model comparison age- sex-matched Bmi-1(+/+) littermates. Bmi-1 is member polycomb-repressive complex family that promotes stem self-renewal expressed by both cells transit-amplifying (TA) crypt. acute (6 h) chronic (11 d) proliferative responses human (Gly(2))GLP-2 TA zone, but not active or reserve zones, were impaired haploinsufficiency. Similarly, regeneration after 10-Gy irradiation reduced animals. Despite these findings, GLP-2 treatment enhanced overall growth mice, as demonstrated increases small weight per body length crypt-villus axis, association decreased apoptosis an adaptive increase epithelial migration rate. results studies therefore demonstrate required for effects physiological pathological setting, mediates, at least part, kinetics zone.