Altered expression of iron-regualtory genes in an animal model of cholestasis

Sobbe, A. L., Bridle, K.R., Fletcher, L. and Crawford, D, H. G. (2010). Altered expression of iron-regualtory genes in an animal model of cholestasis. In: Australian Gastroenterology Week 2010. Australian Gastroenterology Week 2010, Gold Coast, QLD, Australia, (A-8-A-8). 20-23 October 2010. doi:10.1111/j.1440-1746.2010.06450.x


Author Sobbe, A. L.
Bridle, K.R.
Fletcher, L.
Crawford, D, H. G.
Title of paper Altered expression of iron-regualtory genes in an animal model of cholestasis
Conference name Australian Gastroenterology Week 2010
Conference location Gold Coast, QLD, Australia
Conference dates 20-23 October 2010
Proceedings title Australian Gastroenterology Week 2010   Check publisher's open access policy
Journal name Journal of Gastroenterology and Hepatology   Check publisher's open access policy
Place of Publication Richmond, VIC, Australia
Publisher Wiley-Blackwell Publishing Asia
Publication Year 2010
Year available 2010
Sub-type Published abstract
DOI 10.1111/j.1440-1746.2010.06450.x
ISSN 0815-9319
1440-1746
Volume 25
Issue Supp. 3
Start page A-8
End page A-8
Total pages 1
Collection year 2011
Language eng
Formatted Abstract/Summary
Background:
Excess iron deposition is present in up to a third of liver explants from patients without hereditary hemochromatosis1. It is well established that iron-related genes are dysregulated in hepatocellular disease however there is little data to suggest that iron homeostasis is altered in cholestatic liver disease. Bile salts and infl ammation, important mediators of cholestatic injury, have been shown to modulate hepcidin (HAMP) levels. Thus, we investigated the expression of iron-regulatory genes in Mdr2−/− mice, an animal model of cholestatic liver injury, to determine if iron homeostasis is altered in this model.

Methods:
Wild type and Mdr2−/− mice were sacrifi ced at 3, 5, 8, 12 and 16 weeks of age. Liver expression of ron-regulatory genes (HAMP1, transferrin receptor 1 and 2, and ferroportin,) was assessed using real time RT-PCR. Basic transcription factor 3 (BTF3) was used as a housekeeper gene.

Results:
HAMP1 mRNA expression was decreased by 15%, 30%, 60%, 40% and 30% at 3, 5, 8, 12 and 16 weeks respectively in Mdr2−/− when compared to wild type (p < 0.05 from 5 weeks). Transferrin receptor 1 TFR1) was signifi cantly elevated from 3 weeks to 16 weeks of age in Mdr2−/− mice when compared to wild type (3W: 1.57 ± 0.15 vs 0.69 ±
0.13; 5W: 1.41 ± 0.13 vs. 0.43 ± 0.04; 8W: 1.57 ± 0.23 vs 0.24 ± 0.07; 12W: 0.87 ± 0.12 vs 0.39 ± 0.02; 16W: 0.89 ± 0.09 vs 0.38 ± 0.06 for Mdr2−/− and wild type respectively). In contrast, expression of transferrin receptor 2 (TFR2) in Mdr2−/−s was decreased approximately 1.5-fold from 5 weeks of age (p < 0.05 at 5, 12 and 16 weeks). Ferroportin expression remained relatively unchanged in Mdr2−/− when compared to controls however there was a trend towards decreased expression in older Mdr2−/− animals.

Conclusions:
The gene expression patterns seen in the Mdr2−/− model are consistent with an iron defi cient phenotype and/or dysregulated iron homeostasis. This phenotype favours iron accumulation and does not explain the paucity of iron loading in biliary disease.
© 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd

Keyword Gastroenterology & Hepatology
Q-Index Code CX
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Special Issue: Australian Gastroenterology Week 2010. Published under Basic Science.

Document type: Conference Paper
Collections: Non HERDC
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Created: Sun, 09 Jan 2011, 00:04:18 EST