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Increased expression of HGF and c-met in rat small intestine during recovery from methotrexate-induced mucositis.

Increased expression of HGF and c-met in rat small intestine during recovery from methotrexate-induced mucositis.

Authors :
Xian, C J
Couper, R
Howarth, G S
Read, L C
Kallincos, N C
Source :
British Journal of Cancer; 2/15/2000, Vol. 82 Issue 4, p945, 8p
Publication Year :
2000

Abstract

Chemotherapy or radiotherapy often cause mucosal damage in the gut (gut mucositis) in cancer patients. As a step to investigate mechanisms underlying subsequent intestinal repair, we have examined the expression profiles of hepatocyte growth factor (HGF) and its receptor c-met, two molecules previously implicated in tissue repair, in comparison to the histopathological and proliferative changes in a rat model of methotrexate-induced small intestinal mucositis. Histological analysis of the intestinal specimens revealed crypt loss and villus atrophy with damage maximal on day 5 after methotrexate injection, and normalization of mucosal structure commencing on day 6. Crypt cell proliferation was decreased dramatically on day 3, normalized on day 4 and up-regulated on days 5 and 6. HGF and c-met protein/mRNA expression was up-regulated between days 4 and 7, with the mRNA co-localizing to the crypt and lower villus epithelium. Therefore, following methotrexate injection, a decrease in crypt cell proliferation preceded histological damage, and conversely, crypt cell hyperproliferation preceded mucosal regeneration. Up-regulation of HGF and c-met coincided with crypt hyperproliferation and mucosal recovery, suggesting a role for HGF in intestinal repair following acute injury. The crypt epithelial localization of HGF and c-met implies an autocrine or paracrine mechanism of HGF action. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00070920
Volume :
82
Issue :
4
Database :
Complementary Index
Journal :
British Journal of Cancer
Publication Type :
Academic Journal
Accession number :
8877089
Full Text :
https://doi.org/10.1054/bjoc.1999.1023