TITLE:
Differences in the expression of hepatocyte growth factor in acute and chronic bowel inflammation—Implications for diagnosis?
AUTHORS:
Johanna Lönn, Sravya Nakka, Hans Olsson, Torbjörn Bengtsson, Sven Almer, Fariba Nayeri
KEYWORDS:
Diarrhoea; Ulcerative Colitis; Dextran Sulphate; HGF; HSPG; Calprotectin
JOURNAL NAME:
Advances in Bioscience and Biotechnology,
Vol.4 No.8B,
August
8,
2013
ABSTRACT: Background:
Hepatocyte growth factor (HGF) acts as an acute phase protein with regenerative
properties. HGF is produced systemically and locally during inflammation but
exhibits decreased binding affinity to heparan sulphate proteoglycan (HSPG)/glycosaminoglycan during chronic inflammation. We previously observed a high faecal concentration and
binding affinity of HGF to HSPG during acute gastroenteritis. High faecal
concentrations of calprotectin and HGF have been reported in chronic
inflammatory bowel disease (IBD). Methods: Stool samples from patients with
ulcerative colitis in remission (n = 11) or exacerbation (n = 5), microscopic
colitis (n = 11), colon cancer (n = 6), or acute gastroenteritis caused by Clostridium difficile (n = 20), as
well as healthy controls (n = 7), were analysed for the presence of HGF by
ELISA, surface plasmon resonance, SDS-PAGE, and Western blot. Then in two
patients with ulcerative colitis exacerbation and C. difficile infection, the expression of HGF and calprotectin was
studied in colonic biopsies. Results: The faecal concentration of HGF was
significantly higher in patients with ulcerative colitis compared to the
other groups. The binding affinity to dextran was lower in all groups compared
to acute inflammation. HGF receptor binding was similar across groups. In a patient with
concomitant C. difficile infection and distal ulcerative
colitis, HGF was highly expressed in the part of the bowel unaffected by
ulcerative colitis, but no expression was found at the site of chronic
inflammation. In the patient with total colitis the biopsies showed low
expression of HGF. The areas with chronic inflammation exhibited infiltrating
calprotectin-stained neutrophils. Conclusion:
HGF is produced locally during inflammation of the bowel. The HGF produced
during acute inflammation or exacerbations of chronic inflammation by the
unaffected area shows binding affinity to glucosaminoglycans. Measuring HGF
binding in faeces and biopsies may be a tool for differentiating between
acute and chronic bowel inflammation, which should be assessed thoroughly in
future studies.