Novel mfgl2 antisense plasmid inhibits murine fgl2 expression and ameliorates murine hepatitis virus type 3-induced fulminant hepatitis in BALB/cJ mice.
Our previous reports, both experimental and human studies, have shown the importance of fibrinogen-like protein-2 (fgl2) prothrombinase in the development of fulminant viral hepatitis, a disease with a mortality of more than 80% in cases lacking immediate organ transplantation. To interfere with this potentially effective target, a 322-bp mouse fgl2 (mfgl2) antisense plasmid complementary to the exon 1 sequence of the gene, including the translation initiation site AUG, was successfully constructed. A dose-dependent inhibitory effect on mfgl2 expression by mfgl2 antisense plasmid was observed in interferon-gamma-treated RAW 264.7 cells. On hydrodynamic delivery, mfgl2 antisense plasmid significantly reduced mfgl2 expression in vivo; markedly ameliorated inflammatory cell infiltration, fibrin deposition, and hepatocyte necrosis; prolonged the survival time period; and elevated the survival rate among BALB/cJ mice with murine hepatitis virus type 3-induced fulminant hepatitis. This study may provide an effective way to interfere with the potential therapeutic target fgl2 gene for fulminant viral hepatitis and other diseases with similar pathological characteristics of microcirculation disorders, including acute rejection of xeno- or allograft transplantation and fetal loss syndrome, in which studies show fgl2 plays an important role.
Zhu
Chuanlong
C
Laboratory of Infectious Immunology, Department of Infectious Disease, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Sun
Yi
Y
Luo
Xiaoping
X
Yan
Weiming
W
Xi
Dong
D
Ning
Qin
Q
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D016373:DNA, Antisense / Q000008:administration & dosage* / Q000235:genetics; D004195:Disease Models, Animal; D005340:Fibrinogen / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D015316:Genetic Therapy / Q000379:methods*; D006524:Hepatitis, Viral, Animal / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008099:Liver / Q000187:drug effects / Q000473:pathology / Q000821:virology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D006517:Murine hepatitis virus / Q000235:genetics* / Q000378:metabolism; D010957:Plasmids / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D015996:Survival Rate
D016373:DNA, Antisense; C490637:Fgl2 protein, mouse; D005340:Fibrinogen