Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 36, Issue 3, Pages 1026-1036Publisher
KARGER
DOI: 10.1159/000430276
Keywords
Cirrhosis; MicroRNAs; miR-22; Carbon tetrachloride (CCl4); Bone morphogenic protein 7 (BMP7); Antisense
Categories
Funding
- Wang Baoen Foundation for Liver Fibrosis Research [434510Z0A10]
- National Natural Science Foundation of China [81371799]
Ask authors/readers for more resources
Background/Aims: New strategies for the prevention and treatment of cirrhosis are urgently needed for improving therapeutic outcome. A role of microRNAs (miRNAs) in the pathogenesis of cirrhosis has been recently acknowledged, whereas the exact involved miRNAs as well as the associated molecular signaling pathways have not been determined. Specifically, the studies on the relationship between miR-22 and bone morphogenic protein 7 (BMP7) in the development of cirrhosis are lacking. Methods: We examined the correlation of the levels of miR-22 and bone morphogenic protein 7 (BMP7) in the liver biopsies from patients with cirrhosis. We examined overexpression or suppression of miR-22 on BMP7 in hepatocytes. We examined the binding of miR-22 to the 3'-UTR of BMP7 mRNA. Finally, in a carbon tetrachloride (CCl4)-induced cirrhosis model in mice, we gave mice adeno-associated viruses carrying antisense of miR-22, and examined its effects on BMP7 levels and the hallmarks of cirrhosis. Results: The levels of miR-22 and BMP7 in the liver biopsies from patients were strongly and inversely correlated. MiR-22 inhibited BMP7 expression in hepatocytes, through directly binding the 3'-UTR of BMP7 mRNA. Expression of antisense miR-22 significantly attenuated the levels of liver fibrosis, portal hypertension and sodium retention caused by CCl4, possibly through upregulation of BMP7. Conclusions: MiR-22 promotes the development of cirrhosis through BMP7 suppression. Copyright (C) 2015 S. Karger AG, Basel
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available