PMID- 11310823
OWN - NLM
STAT- MEDLINE
DCOM- 20010503
LR  - 20230216
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 81
IP  - 3
DP  - 2001 Mar
TI  - Ulcerative proctitis, rectal prolapse, and intestinal pseudo-obstruction in 
      transgenic mice overexpressing hepatocyte growth factor/scatter factor.
PG  - 297-305
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) can stimulate growth of 
      gastrointestinal epithelial cells in vitro; however, the physiological role of 
      HGF/SF in the digestive tract is poorly understood. To elucidate this in vivo 
      function, mice were analyzed in which an HGF/SF transgene was overexpressed 
      throughout the digestive tract. Nearly a third of all HGF/SF transgenic mice in 
      this study (28 of 87) died by 6 months of age as a result of sporadic intestinal 
      obstruction of unknown etiology. Enteric ganglia were not overtly affected, 
      indicating that the pathogenesis of this intestinal lesion was different from 
      that operating in Hirschsprung's disease. Transgenic mice also exhibited a rectal 
      inflammatory bowel disease (IBD) with a high incidence of anorectal prolapse. 
      Expression of interleukin-2 was decreased in the transgenic colon, indicating 
      that HGF/SF may influence regulation of the local intestinal immune system within 
      the colon. These results suggest that HGF/SF plays an important role in the 
      development of gastrointestinal paresis and chronic intestinal inflammation. 
      HGF/SF transgenic mice may represent a useful model for the study of molecular 
      mechanisms associated with a subset of IBD and intestinal pseudo-obstruction. 
      Moreover, our data identify previously unappreciated side effects that may be 
      encountered when using HGF/SF as a therapeutic agent.
FAU - Takayama, H
AU  - Takayama H
AD  - First Department of Internal Medicine, Gunma University School of Medicine, 
      Maebashi, Japan.
FAU - Takagi, H
AU  - Takagi H
FAU - Larochelle, W J
AU  - Larochelle WJ
FAU - Kapur, R P
AU  - Kapur RP
FAU - Merlino, G
AU  - Merlino G
LA  - eng
GR  - DK52530/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Interleukin-2)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
SB  - IM
MH  - Animals
MH  - Colitis, Ulcerative/mortality/*pathology
MH  - Female
MH  - Gene Expression
MH  - Hepatocyte Growth Factor/*genetics
MH  - Humans
MH  - Interleukin-2/genetics
MH  - Intestinal Pseudo-Obstruction/mortality/*pathology
MH  - Intestine, Large/pathology/physiology
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - Proto-Oncogene Proteins c-kit/genetics
MH  - Rectal Prolapse/mortality/*pathology
MH  - Survival Rate
EDAT- 2001/04/20 10:00
MHDA- 2001/05/05 10:01
CRDT- 2001/04/20 10:00
PHST- 2001/04/20 10:00 [pubmed]
PHST- 2001/05/05 10:01 [medline]
PHST- 2001/04/20 10:00 [entrez]
AID - S0023-6837(22)01996-1 [pii]
AID - 10.1038/labinvest.3780238 [doi]
PST - ppublish
SO  - Lab Invest. 2001 Mar;81(3):297-305. doi: 10.1038/labinvest.3780238.