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Application of zinc finger protein 307 (ZNF307) in treating myocardial hypertrophy

A technology of zinc finger protein and cardiac hypertrophy, applied in drugs for relieving and/or treating cardiac hypertrophy, preparation prevention, function and application field of zinc finger protein 307 (ZNF307) in the treatment of cardiac hypertrophy, to inhibit cardiac hypertrophy , anti-cardiac fibrosis, myocardial hypertrophy, and the effect of protecting heart function

Active Publication Date: 2015-12-30
WUHAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the mechanism of cardiac hypertrophy has not been fully elucidated

Method used

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  • Application of zinc finger protein 307 (ZNF307) in treating myocardial hypertrophy
  • Application of zinc finger protein 307 (ZNF307) in treating myocardial hypertrophy
  • Application of zinc finger protein 307 (ZNF307) in treating myocardial hypertrophy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0077] [Example 1] Expression of ZNF307 in the hearts of normal people and patients with cardiomyopathy

[0078] SDS-PAGE-immunoblotting test (Westernblot) was performed on proteins extracted from the hearts of normal human hearts (individuals donated by non-cardiac causes of death) and hearts of patients with dilated cardiomyopathy (recipients replaced by patients undergoing heart transplantation, DCM). , combined with antibodies that specifically recognize ZNF307 protein and cardiomyocyte hypertrophy markers ANP (Millipore, AB2232) and Myh7 (santacruz, sc53090) to detect the expression of ZNF307 (unknown), and GAPDH (BioworldTechnology, MB001) was used as an internal reference. Test results such as figure 1 As shown, the expressions of cardiomyocyte hypertrophy markers ANP and Myh7 were significantly up-regulated in the hearts of patients with dilated cardiomyopathy, and the expression of ZNF307 was also significantly up-regulated ( figure 1 A).

Embodiment 2

[0079] [Example 2] Expression of ZNF307 in wild-type mouse Sham group and AB operation 4W, 8W hearts

[0080] 1. The myocardial hypertrophy model adopts aortic arch coarctation surgery, and the operation process of the model is as follows:

[0081] 1.1 Preoperative preparation

[0082] (1) Anesthesia: First weigh the mice, calculate the required amount of anesthetic (3% pentobarbital sodium) according to 90 mg / kg body weight, inject intraperitoneally, and record the injection time point. There is no obvious reaction between tail and toe pinching and the mouse is in good condition. This is the standard for successful anesthesia (generally there is no obvious reaction about 10 minutes after injection, and the mouse has a reaction to pinch toe about 50 minutes after anesthesia, and about 30 minutes after anesthesia is the best operation time).

[0083] (2) Preparation of the operation area: the skin of the left chest, left chest and armpit of the left forelimb of the mouse was r...

Embodiment 3

[0093] [Example 3] The effect of ZNF307 interference (AdshZNF307) and overexpression (AdZNF307) adenovirus on the expression of ZNF307 in AngII-stimulated primary cardiomyocytes

[0094] 1. Primary neonatal SD rat cardiomyocyte culture

[0095] Sprague-Dawley neonatal rat cardiomyocytes were isolated and cultured for 1 day, and the medium was changed after 48 hours of primary cardiomyocytes.

[0096] 2. Effect of ZNF307 interference (AdshZNF307) and overexpression (AdZNF307) adenovirus on AngII-induced cardiomyocyte hypertrophy model

[0097] AdshRNA (adenovirus containing shRNA (silencing RNA), used as a control), AdshZNF307 (adenovirus containing shRNA-ZNF307 (silencing RNA-ZNF307 fusion protein)), AdGFP (adenovirus containing GFP (green fluorescent protein), used as control) and AdZNF307 (adenovirus containing GFP-ZNF307 green fluorescent protein-ZNF307 fusion protein) adenovirus 10MOIs respectively infected primary cardiomyocytes cultured for 3 days, 12 hours later with 1...

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Abstract

The invention discloses application of zinc finger protein 307 (ZNF307) in protecting heart function, resisting cardiac fibrosis and / or preventing and relieving and / or treating myocardial hypertrophy and belongs to the field of gene application. The circumstance that expression of ZNF307 in a model occurring myocardial hypertrophy is remarkably lowered when compared with that of a normal group is determined; inhibition of ZNF307 expression remarkably promotes myocardial hypertrophy and fibrosis and deteriorates the heart function while promotion of overexpression of the ZNF307 remarkably inhibits myocardial hypertrophy and fibrosis and protects the heart function. The ZNF307 can serve as a drug target to be used for screening drug for protecting heart function, resisting cardiac fibrosis and / or preventing and relieving and / or treating myocardial hypertrophy; the ZNF307 can serve as a target gene in gene treatment to be used for designing and preparing drug and / or biological preparations for protecting heart function, resisting cardiac fibrosis and / or preventing and relieving and / or treating myocardial hypertrophy, and a novel effective approach is provided for treatment of myocardial hypertrophy.

Description

technical field [0001] The invention belongs to the field of gene function and application, and particularly relates to the function and application of a zinc finger protein 307 (ZNF307) in the treatment of cardiac hypertrophy, specifically the application in the preparation of drugs for preventing, alleviating and / or treating cardiac hypertrophy. Background technique [0002] Cardiac hypertrophy (hypertrophic cardiomyopathy, HCM) is a compensatory response of the myocardium to long-term pressure or increased volume load, which is mainly characterized by increased cardiomyocyte volume and extracellular matrix[1-3]. Although myocardial hypertrophy is initially a compensatory mechanism, long-term persistent pressure or volume loading can cause decompensation, leading to dilated cardiomyopathy, heart failure, and even sudden death[4,5]. Myocardial hypertrophy has become an independent risk factor for cardiovascular diseases such as heart failure, greatly increasing the morbidit...

Claims

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Application Information

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IPC IPC(8): A61K38/17A61K48/00A61P9/00C12Q1/68G01N33/68
Inventor 李红良张志仁于长江张晓晶
Owner WUHAN UNIV
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