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https://hdl.handle.net/2440/11759
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Type: | Journal article |
Title: | Increased expression of HGF and c-met in rat small intestine during recovery from methotrexate-induced mucositis |
Author: | Xian, C. Couper, R. Howarth, G. Read, L. Kallincos, N. |
Citation: | British Journal of Cancer, 2000; 82(4):945-952 |
Publisher: | Churchill Livingstone |
Issue Date: | 2000 |
ISSN: | 0007-0920 1532-1827 |
Statement of Responsibility: | CJ Xian, R Couper, GS Howarth, LC Read and NC Kallincos |
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. |
Keywords: | hepatocyte growth factor HGF c-met methotrexate intestinal mucositis regeneration |
Rights: | © 2000 Cancer Research Campaign |
DOI: | 10.1054/bjoc.1999.1023 |
Published version: | http://dx.doi.org/10.1054/bjoc.1999.1023 |
Appears in Collections: | Aurora harvest 2 Physiology publications |
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