Enhanced survival and mucosal repair after dextran sodium sulfate-induced colitis in transgenic mice that overexpress growth hormone

被引:211
作者
Williams, KL [1 ]
Fuller, CR
Dieleman, LA
DaCosta, CM
Haldeman, KM
Sartor, RB
Lund, PK
机构
[1] Univ N Carolina, Dept Cell & Mol Physiol, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Dept Pediat, Chapel Hill, NC 27599 USA
[3] Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA
[4] Univ N Carolina, Ctr Gastrointestinal Biol & Dis, Chapel Hill, NC 27599 USA
关键词
D O I
10.1053/gast.2001.22470
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Aims: Growth hormone (GH) is used as therapy for inflammatory bowel disease (IBD), but the specific effects on intestine are unknown. Transgenic mice overexpressing GH (MT1-bGH-TG) were used to test whether increased plasma GH levels alter inflammation or crypt damage during dextran sodium sulfate (DSS)induced colitis, Methods: MT1-bGH-TG and wild-type (WT) littermates were given 3% DSS for 5 days followed by up to 10 days of recovery, Colitis and epithelial cell proliferation were evaluated histologically. Plasma insulin-like growth factor (IGF)-I and colonic IGF-I, interleukin (IL)-1 beta, and intestinal trefoil factor (ITF) messenger RNAs (mRNAs) were measured. Results: DSS induced similar disease onset in MT1-bGH-TG and WT, More MT1-bGH-TG survived than WT. By recovery day 7, MT1-bGH-TG had less inflammation and crypt damage, elevated plasma IGF-I, and increased colonic ITF expression relative to WT. Colonic IL-1 beta was elevated in DSS-treated MT1-bGH-TG and WT, but IL-1 beta mRNA abundance correlated with disease only in WT, MT1-bGH-TG showed earlier increases in epithelial cell proliferation than WT during recovery but only WT showed atypical repair. Conclusions: GH does not alter susceptibility to acute DSS-induced colitis but enhances survival, remission of inflammation, and mucosal repair during recovery, GH therapy may be beneficial during active IBD by improving mucosal repair.
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页码:925 / 937
页数:13
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