Application of miRNA-378 in treatment of fatty liver

A technology of mirna-378 and .mirna-378 is applied in the field of miRNA and its mechanism of action in the treatment of fatty liver, which can solve the problems of poor patient compliance and aggravation of liver dysfunction.

Active Publication Date: 2016-06-01
SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, since lowering blood lipids is also necessary to inhibit fat deposition in the liver, some lipid-lowering drugs may even aggravate liver dysfunction, and lifestyle changes are too subjective, and patients' compliance is not good enough
Therefore, so far, there is no effective method that can simultaneously reduce blood lipids and rapidly reduce fat accumulation in the liver, thereby treating fatty liver.

Method used

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  • Application of miRNA-378 in treatment of fatty liver
  • Application of miRNA-378 in treatment of fatty liver
  • Application of miRNA-378 in treatment of fatty liver

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0198] Example 1 The effect of overexpression of miR-378 on the content of TG in the liver of mice

[0199] Using common methods, miR-378 was overexpressed in mouse liver by adenovirus, and the qPCR results showed that miR-378 was overexpressed more than 50 times ( figure 1 ).

[0200] The liver TG content was measured. The results showed that the liver TG content decreased significantly after miR-378 was infected; H&E staining and oil red staining were performed on the liver. The results also showed that the liver overexpressing miR-378 can reduce the liver TG content.

Embodiment 2

[0201] Example 2 miR-378 affects liver TG content by targeting p110α

[0202] 2.1 Through bioinformatics analysis, dozens of potential miR-378 target proteins were screened. These target proteins may be involved in the regulation of liver TG by miR-378. Then through westernblot, the mouse liver protein was tested and found that after the liver was infected with miR-378, among the potential target proteins that were screened, the protein level of p110α, an important factor involved in the liver insulin signaling pathway, had the most significant decline.

[0203] 2.2 The sequence of p110α was further studied, and it was found that there is a site in the 3’UTR sequence of p110α that may bind to miR-378 ( figure 2 a). Then, the potential miR-378 binding site in the 3'UTR sequence of p110α was cloned, and then through double fluorescence experiments in cells in vitro, it was found that miR-378 could significantly inhibit the activity of p110α-3'UTR. This indicates that miR-378 can di...

Embodiment 3

[0206] Example 3 miR-378 improves liver fat accumulation

[0207] The overexpression of miR-378 in ob / ob mouse liver by adenovirus can effectively reduce the TG content in the liver ( image 3 ). The subsequent H&E and oil red staining results are also in line with the previous results. In conclusion, overexpression of miR-378 in ob / ob mouse liver can effectively improve liver fat accumulation.

[0208] discuss

[0209] Insulin signaling pathway mainly refers to the signal transduction process of insulin by activating insulin receptor, insulin receptor substrate, phosphatidylinositol 3-kinase and protein kinase B, which plays an important role in regulating the level of triglycerides in the liver. The excessive accumulation of liver triglycerides is often caused by abnormal liver insulin signaling pathways. The present invention discovers microRNAs that can affect key nodes of the insulin signal pathway, so as to have a clearer understanding of the insulin signal pathway and provi...

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Abstract

The present invention discloses application of miRNA-378 in treatment of fatty liver. In particular, the miRNA-378 in liver is confirmed to be an insulin signal pathway regulating core element. When the miR-378 is overexpressed in mouse liver, mouse lipid metabolism steady state is enhanced, and is mainly shown as decreased liver TG content, wherein the miR-378 can perform functions through inhibition of insulin signal pathway key protein p110 alpha, so that inhibition of the expression of the p110 alpha by the overexpression of the miR-378 in the liver can be a new therapeutic strategy for liver lipid accumulation.

Description

Technical field [0001] The invention belongs to the field of treatment of metabolic diseases. Specifically, it relates to a miRNA for treating fatty liver and its mechanism of action. Background technique [0002] The liver is an important metabolic organ of the human body. It can sense a variety of signals from hormones, nerve impulses, nutritional and metabolic factors and perform specific functions. The liver plays a very important role in regulating the body's glucose and lipid balance. Fatty liver is a disease caused by excessive accumulation of triglycerides (TG) in liver cells due to the disorder of body lipid metabolism. In recent years, with the changes in people's diet, the incidence of fatty liver has increased year by year. Long-term liver lipid deposition may cause abnormal liver function, and severe cases can lead to liver fibrosis, cirrhosis, and even liver failure. [0003] At present, the treatment of fatty liver mainly relies on lowering blood lipids or lifest...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K48/00A61P3/06
Inventor 应浩刘威
Owner SHANGHAI INST OF BIOLOGICAL SCI CHINESE ACAD OF SCI
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