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Uses of miR-431 in preparation of muscular disease treatment medicines

A mir-431, 1.mir-431 technology, applied in the medical field, can solve the problems of survival, self-renewal and poor migration, host immune rejection and so on

Active Publication Date: 2015-01-28
THE INST OF BASIC MEDICAL SCI OF CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, there are the following problems, firstly, the immune rejection of the host, and secondly, the survival, self-renewal and migration after transplantation of satellite cells are relatively poor

Method used

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  • Uses of miR-431 in preparation of muscular disease treatment medicines
  • Uses of miR-431 in preparation of muscular disease treatment medicines
  • Uses of miR-431 in preparation of muscular disease treatment medicines

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0062] Example 1. Myostatin negatively regulates the expression of miR-431 through the Ras / Raf / Mek / Erk signaling pathway

[0063] 1. Screening miR-431 negatively regulated by myostatin

[0064] miR-431, which was upregulated in myostatin knockout mouse skeletal muscle tissue, was selected as a candidate miRNA to study its function and self-expression regulation. During the five stages of skeletal muscle development, the expression of miR-431 in myostatin knockout mice was higher than that in wild-type mice (such as figure 1 ). Different developmental stages (E15.5, 4 weeks, 10 weeks, 16 weeks) from myostatin gene knockout mice (purchased from: Nanjing Institute of Model Animals) and wild-type sibling mice (the littermate control of gene knockout mice) Total RNA was extracted from skeletal muscle tissues of 40 weeks and 40 weeks), and miRNA expression profiling chip method was used to screen and identify miRNAs differentially expressed in skeletal muscle tissues between myost...

Embodiment 2

[0087] Example 2. miR-431 is highly enriched in skeletal muscle tissue and its expression level increases with the differentiation of C2C12 cells and satellite cells.

[0088] To study the function of miR-431 in skeletal muscle, the expression profile of miR-431 was studied. First, Northern blot was used to measure the expression abundance of miR-431 in various tissues and organs of 8-week-old mice. In order to further determine the expression of miR-431, the expression of miR-431 in different differentiation states of C2C12 cells was detected, and the expression of miR-431 in different stages of skeletal muscle satellite differentiation was also detected.

[0089] miR-431 is highly enriched in skeletal muscle tissue

[0090] Experimental process: 8-week-old mice were selected, and the lung, liver, heart, spleen, skeletal muscle, kidney, pancreas, small intestine, brain, and stomach tissues were collected and RNA was firstly extracted and then Northern Blot hybridization was ...

Embodiment 3

[0113] Example 3. miR-431 promotes C2C12 cell differentiation.

[0114] To study the function of miR-431 in skeletal muscle, the function of miR-431 was detected in C2C12 cells. First, a stable transfection cell line overexpressing miR-431 (about 60 times) was constructed in the C2C12 cell line, and the following functional tests were performed using the established C2C12 cell line overexpressing miR-431.

[0115] Cells stably transfected with mi-431 were first planted at a certain density, and the differentiation medium was changed after 24 hours of proliferation. After 24 hours and 36 hours of differentiation, the early differentiation molecular marker molecule Myogenin (Myogenin) and the late differentiation marker molecule were detected respectively. Expression of MHC. By immunofluorescent staining of cells, it was found that after 24 hours of differentiation, overexpression of miR-431 significantly increased the number of myogenin-positive cells, and at the same time the...

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Abstract

The invention relates to a use of miR-431 in the preparation of muscular disease treatment medicines, concretely relates to functions of miR-431 in skeletal muscle stem cells and muscular disease treatment, especially relates to a use of miR-431 in muscle injuries and muscular dystrophy, and also relates to a use of miR-431 in the preparation of skeletal muscle stem cell activation, proliferation and differentiation promotion medicines, and an miR-431-containing medicinal composition for treating muscular diseases.

Description

technical field [0001] The present invention relates to the field of medicine, in particular to the use of miR-431 in the treatment of muscle diseases, especially muscle damage and muscular dystrophy. Background technique [0002] Skeletal muscle plays a very important role in the life activities of organisms. Not only does it perform locomotor and support functions, but it is also an important metabolic organ. Substances such as sugar and lipid ingested by the body are metabolized in the skeletal muscle to produce energy, which plays a very important role in maintaining the stable state of the whole body. Patients with many diseases, such as tumors, HIV infection, and chronic heart failure, are often accompanied by symptoms of gradual loss of skeletal muscle in the late stage. In addition, skeletal muscle is also an important endocrine organ, secreting some regulatory factors, such as myostatin (Myostatin), IL-6, IL-8, IL-15 and FGF21. In addition to regulating the growt...

Claims

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Application Information

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IPC IPC(8): A61K48/00A61P21/00
Inventor 朱大海武日茂翟丽丽张勇
Owner THE INST OF BASIC MEDICAL SCI OF CHINESE ACAD OF MEDICAL SCI
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