Intracolonically administered adeno-associated virus-bone morphogenetic protein-7 ameliorates dextran sulphate sodium-induced acute colitis in rats.
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.
Department of Gastroenterology, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China. haozhm@yahoo.com.cn
Zhiming
Z
Hao
Xiaofei
X
Yang
Yifei
Y
Lv
Shuang
S
Li
Bibek Kumar
BK
Purbey
Houqiang
H
Su
D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control / Q000628:therapy*; D003106:Colon / Q000187:drug effects / Q000473:pathology; D000229:Dependovirus / Q000235:genetics; D016264:Dextran Sulfate / Q000633:toxicity; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms
D055419:Bone Morphogenetic Protein 7; D016264:Dextran Sulfate