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Regulating function of MR-1 gene in myocardial hypertrophy

A technique for cardiac hypertrophy and MR-1, which is used in gene therapy, cardiovascular system diseases, genetic material components, etc.

Inactive Publication Date: 2007-08-22
MEDICINE & BIOENG INST OF CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the role of AngII in the human body is multifaceted. As a new gene, how MR-1 aggravates myocardial hypertrophy through AngII has not been reported so far.

Method used

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  • Regulating function of MR-1 gene in myocardial hypertrophy
  • Regulating function of MR-1 gene in myocardial hypertrophy
  • Regulating function of MR-1 gene in myocardial hypertrophy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0064] : Establishment of MR-1 transgenic mouse model

[0065] Acquisition of MR1 gene: PCR reaction was carried out with primer A and primer B using a human skeletal muscle cDNA library (purchased from Clontech) as a template.

[0066] Primer A: 5'-ATTAGAATTCATGGCGGCGGTGGTAGCTGCT-3' (EcoRI)

[0067] Primer B: 5'-ATTAGTCGACTCAGGTCTGCACCCCAGACCC-3'(SalI)

[0068] The obtained PCR product contains MR1 ​​gene, which is composed of 425 nucleotides and encodes 142 amino acids. This fragment was inserted into the vector pIRES2-GFP (Clontech. Company) with EcoRI and SalI restriction sites to construct the recombinant vector pIRES2-GFP-hMR-1. Then the recombinant vector was cut into a linear shape with SphI, and the 4.8 kb fragment was recovered by agarose gel electrophoresis, and purified by Nuclespin column (Clontech. Company). The linear DNA fragment containing MR1 gene was injected into 300 mouse fertilized eggs by microinjection technique, and 108 newborn mice were obtained. ...

Embodiment 2

[0070] : Transgenic mice perfused with angiotensin AngII

[0071] Take 14 MR1 transgenic mice and 13 non-transgenic mice as controls. Dissolve AngII in acetic acid to make (0.001-0.005mol / l) solution, subcutaneously inject 0.1-0.3mg AngII per kilogram of body weight per day, and perfuse it for 1-2 weeks. In addition, 14 transgenic mice and 13 non-transgenic mice were used as the sham operation group for control.

Embodiment 3

[0072] : Western blot hybridization detection of high expression of MR1 in transgenic mice

[0073] Extract transgenic mouse myocardial tissue protein, about 50 micrograms were electrophoresed in 10% polyacrylamide protein gel, transferred to nitrocellulose membrane, and MR1 antibody (self-made) and GAPDH antibody were used as internal references (Kangcheng Biological Company) for hybridization, and then used two The anti-peroxidase-conjugated antibody was used for color development and detected with a chemiluminescent kit (Amersham, Inc.). The technique of western blot hybridization showed that the MR1 gene was obviously highly expressed in the MR1 transgenic mice, while the MR1 gene was basically not expressed in the control mice (Figure 2).

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Abstract

The present invention relates to human gene function, and is especially MR-1 gene function relevant to myocardial hypertrophy. It is shown through animal in vivo experiment that the high expression of this gene intensifies the effect of AngII on myocardial hypertrophy, inflammation and fiberosis. It is proven that the function mechanism of MR-1 is the regulation and control on nuclear factor NF-kappa-B signal path and interfering the expression of MR-1 can lower or weaken the induction of AngII on NF-kappa-B. Therefore, it is hopeful that lowering or blocking the expression of MR-1 gene becomes the new target of treating myocardial hypertrophy relevant diseases.

Description

Technical field: [0001] The present invention relates to a human gene function, in particular to the gene function related to cardiac hypertrophy; the present invention also relates to the mechanism of the gene function regulating myocardial function, to clarify the relationship between gene expression and myocardial disease, and to seek the clinical diagnosis of related diseases and treatment laid the foundation. Background technique: [0002] The MR-1 gene is a regulatory gene for myofibrogenesis. The formation of myofibrils is related to a special kind of fibroblasts, which are contractile, can synthesize and degrade extracellular matrix, and have the functions of secreting cytokines, growth factors and inflammatory mediators. Human cardiomyoblasts (fibroblasts) are the source of cardiac hypertrophy and cardiac fibrosis associated with heart failure. The latter is regulated by many factors, such as Myostatin negatively regulates cell proliferation; a large number of stu...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K48/00A61P9/00C12Q1/68
Inventor 王以光李洪亮李天伯折志刚戴文建刘德培孔维佳赫卫清左增艳蒋建东
Owner MEDICINE & BIOENG INST OF CHINESE ACAD OF MEDICAL SCI