MiR-22 Suppresses BMP7 in the Development of Cirrhosis
1Liver Fibrosis Diagnosis and Treatment Center, 302 Hospital of PLA, Beijing, China.
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.
Insights
MicroRNA-22 (miR-22) promotes cirrhosis by suppressing bone morphogenic protein 7 (BMP7). Inhibiting miR-22 in mice reduced liver fibrosis and portal hypertension, suggesting therapeutic potential.
Area of Science:
- Hepatology
- Molecular Biology
- MicroRNA Research
Background:
- Cirrhosis pathogenesis involves microRNAs (miRNAs), but specific miRNAs and pathways remain unclear.
- The relationship between miR-22 and bone morphogenic protein 7 (BMP7) in cirrhosis development is not well-established.
Purpose of the Study:
- Investigate the role of miR-22 in cirrhosis development.
- Determine the molecular link between miR-22 and BMP7 in liver disease.
Main Methods:
- Correlated miR-22 and BMP7 levels in human cirrhotic liver biopsies.
- Assessed miR-22's effect on BMP7 expression and binding in hepatocytes.
- Utilized a carbon tetrachloride (CCl4)-induced mouse cirrhosis model with miR-22 inhibition.
Main Results:
- Inverse correlation found between miR-22 and BMP7 levels in patients.
- miR-22 directly inhibited BMP7 mRNA by binding to its 3'-UTR.
- Inhibition of miR-22 in mice ameliorated liver fibrosis, portal hypertension, and sodium retention.
Conclusions:
- miR-22 promotes cirrhosis development by suppressing BMP7.
- Targeting miR-22 may offer a novel therapeutic strategy for cirrhosis.
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