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

Gastroenterology. 2001 Mar;120(4):925-37. doi: 10.1053/gast.2001.22470.

Abstract

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)-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Colitis / chemically induced
  • Colitis / mortality
  • Colitis / pathology
  • Colitis / physiopathology*
  • Colon / metabolism
  • Dextran Sulfate
  • Growth Hormone / genetics
  • Growth Hormone / pharmacology*
  • Growth Substances / metabolism
  • Insulin-Like Growth Factor I / metabolism
  • Interleukin-1 / genetics
  • Intestinal Mucosa / pathology
  • Intestinal Mucosa / physiopathology*
  • Mice
  • Mice, Transgenic / genetics
  • Mucins*
  • Muscle Proteins*
  • Neuropeptides*
  • Peptides / metabolism
  • RNA, Messenger / metabolism
  • Reference Values
  • Survival Analysis
  • Trefoil Factor-2
  • Trefoil Factor-3
  • Wound Healing / drug effects*

Substances

  • Growth Substances
  • Interleukin-1
  • Mucins
  • Muscle Proteins
  • Neuropeptides
  • Peptides
  • RNA, Messenger
  • TFF3 protein, rat
  • Trefoil Factor-2
  • Trefoil Factor-3
  • Insulin-Like Growth Factor I
  • Growth Hormone
  • Dextran Sulfate