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Murine Colitis Modeling using Dextran Sulfate Sodium (DSS)
Published on: January 19, 2010
Intracolonically administered adeno-associated virus-bone morphogenetic protein-7 ameliorates dextran sulphate
Zhiming Hao1, Xiaofei Yang, Yifei Lv
1Department of Gastroenterology, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China. haozhm@yahoo.com.cn
Background:
The current treatment of ulcerative colitis (UC) is less than ideal and has room for improvement. Bone morphogenetic protein-7 (BMP-7) exerts a protective effect on experimental UC. Hence, we considered that intracolonically (i.c.) administered adeno-associated virus (AAV) delivering BMP-7 might have therapeutic potential for UC.
Methods:
Recombinant AAV type 2 vectors carrying enhanced green fluorescence protein (AAV-EGFP), LacZ (AAV-LacZ) and BMP-7 (AAV-BMP-7) were generated. Bioluminescence imaging, β-galactosidase assay and western blotting were applied to determine the colonic expression of EGFP, LacZ and BMP-7, respectively, after i.c. administration of the AAVs. Disease activity index (DAI) was observed daily during the 7 days of dextran sulphate sodium (DSS) treatment initiated 4 days after i.c. AAV-BMP-7, AAV-LacZ or phosphate-buffered saline. The colonic pathological morphology, mucosal myeloperoxidase (MPO) activity, malondialdehyde content, superoxide dismutase activity and proliferating cell nuclear antigen were determined at the end of DSS treatment.
Results:
When i.c administered to rats, AAV could efficiently transduce the colonic mucosa. Enema with AAV-BMP-7 significantly ameliorated DSS-induced colitis as indicated by reduced DAI, decreased macroscopic and histological scores and declined MPO activity compared to the controls. Furthermore i.c. AAV-BMP-7 significantly prevented oxidant damage and attenuated complementary mucosal cell proliferation in the DSS-treated rat colons.
Conclusions:
Our data demonstrate that i.c. administration of AAV-BMP-7 efficiently mediates the ectopic BMP-7 expression in rat colon and further ameliorates DSS-induced UC in rats, suggesting that i.c. AAV-BMP-7 has the potential to be developed into an alternative therapeutic measure for the treatment of UC.
