Curcumin interrupts leptin-regulated microRNA-122 in hepatic stellate cells in vitro and in vivo
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1Department of Clinical Laboratory, Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), YongHe Road 500, Nantong, Jiangsu, China.
Abstract:
The purpose of this study was to evaluate the effect of curcumin, an active polyphenol, on the leptin induced lowering of miR-122 in Hepatic stellate cells (HSCs) in vivo and an animal model. Gene expression was evaluated by transfection assay, real-time PCR, or Western blot analysis. The liver fibrosis model of leptin deficient mouse was used for in vivo experiment. As a result, curcumin showed inhibitory effect on leptin induced lowering of the miR-122 in HSCs. Curcumin suppressed leptin induced sonic hedgehog (Shh) expression and blocked leptin induced Shh signaling pathway, which was essential for curcumin inhibition of the negative role of leptin in miR-122 expression in HSCs. The influence of curcumin on the negative effect of leptin on miR-122 level was followed by the attenuation of liver fibrosis caused by leptin in leptin-deficient mouse model. In conclusion, curcumin could reduce the decrease of miR-122 level in HSCs induced by leptin and inhibit liver fibrosis induced by leptin. These data may have potential implications to treat with liver fibrosis by elevating the expression of leptin in humans especially obese patients.
Insights
Curcumin inhibits leptin-induced miR-122 reduction in liver cells and suppresses liver fibrosis. This suggests potential therapeutic applications for treating liver fibrosis, particularly in obese patients.
Area of Science:
- Biochemistry
- Molecular Biology
- Hepatology
Background:
- Leptin, a hormone, can negatively regulate miR-122 expression in hepatic stellate cells (HSCs).
- Dysregulation of miR-122 is implicated in the pathogenesis of liver fibrosis.
- Understanding leptin's role in miR-122 modulation is crucial for developing anti-fibrotic strategies.
Purpose of the Study:
- To investigate the effect of curcumin on leptin-induced miR-122 downregulation in HSCs.
- To explore the underlying molecular mechanisms involving the sonic hedgehog (Shh) signaling pathway.
- To evaluate curcumin's efficacy in mitigating leptin-associated liver fibrosis in an animal model.
Main Methods:
- Gene expression analysis using real-time PCR and Western blot.
- In vitro studies involving HSCs.
- In vivo experiments utilizing a leptin-deficient mouse model of liver fibrosis.
Main Results:
- Curcumin demonstrated an inhibitory effect on leptin-induced reduction of miR-122 in HSCs.
- Curcumin suppressed leptin-induced sonic hedgehog (Shh) expression and blocked the Shh signaling pathway.
- Curcumin treatment led to the attenuation of liver fibrosis in the animal model.
Conclusions:
- Curcumin effectively counteracts leptin's negative impact on miR-122 levels in HSCs.
- Curcumin exhibits anti-fibrotic properties by modulating the leptin-Shh signaling axis.
- Elevating leptin expression, potentially with curcumin intervention, may offer a novel therapeutic approach for liver fibrosis, especially in obese individuals.
