Enhanced survival and mucosal repair after dextran sodium sulfate-induced colitis in transgenic mice that overexpress growth hormone.
OBJECTIVE
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)-1beta, 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-1beta was elevated in DSS-treated MT1-bGH-TG and WT, but IL-1beta 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.
Williams
K L
KL
Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7545, USA. klwms@med.unc.edu
Fuller
C R
CR
Dieleman
L A
LA
DaCosta
C M
CM
Haldeman
K M
KM
Sartor
R B
RB
Lund
P K
PK
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000401:mortality / Q000473:pathology / Q000503:physiopathology*; D003106:Colon / Q000378:metabolism; D016264:Dextran Sulfate; D013006:Growth Hormone / Q000235:genetics / Q000494:pharmacology*; D006133:Growth Substances / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics; D007413:Intestinal Mucosa / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D016019:Survival Analysis; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D014945:Wound Healing / Q000187:drug effects*
D006133:Growth Substances; D007375:Interleukin-1; D009077:Mucins; D009124:Muscle Proteins; D009479:Neuropeptides; D010455:Peptides; D012333:RNA, Messenger; C099037:TFF3 protein, rat; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D016264:Dextran Sulfate