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Medical application of encoding gene ESRRA of estrogen-related receptor alpha (ERR alpha)

A technology that encodes genes and estrogens, and is used in medical preparations containing active ingredients, gene therapy, pharmaceutical formulations, etc., to improve liver damage, reduce liver inflammation and fibrosis, and achieve significant effects.

Pending Publication Date: 2021-07-16
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Liver cirrhosis is liver dysfunction caused by tissue structure disorder. At present, there is no cure. The main thing is to detect early and prevent the progress of the disease, especially to prevent the complications of liver cirrhosis.

Method used

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  • Medical application of encoding gene ESRRA of estrogen-related receptor alpha (ERR alpha)
  • Medical application of encoding gene ESRRA of estrogen-related receptor alpha (ERR alpha)
  • Medical application of encoding gene ESRRA of estrogen-related receptor alpha (ERR alpha)

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Palmitic acid induces downregulation of ERRα levels in Huh7 cells

[0044] Western Blot method was used to detect the level of ERRα protein in Huh-7 cells stimulated by palmitic acid.

[0045] Cell culture conditions: Huh-7 cells: DMEM complete medium (containing 10% fetal bovine serum and 1% streptomycin / penicillin) was cultured in a 37°C incubator with 5% CO2.

[0046] Antibody: anti-ERRα (Abcam)

[0047] Cell experiments: Cells with a living cell ratio of more than 90% were used for experiments. In a 3.5 cm cell culture dish, Huh-7 cells were plated at 250,000 per dish, cultured in a 37°C incubator containing 5% CO2, and the original medium was discarded after 12 hours. The experimental group was added with a medium solution containing 1.5mM palmitic acid, and the culture dishes were collected after 3h, 6h, 9h and 12h of stimulation, and stored in a -80°C refrigerator; the control group was added with a medium containing defatted bovine serum albumin at the corresp...

Embodiment 2

[0051] Hepatic ERRα levels are downregulated in a high-fat, high-sugar diet (HFHSD)-induced mouse NASH model

[0052] Animals: 10 male C57BL / 6J mice, SPF grade, 4 weeks old, purchased from Beijing Weitong Lihua. All animals were maintained on a 12-h alternating circadian rhythm with free access to food and drink.

[0053] Reagents: high-fat and high-sugar feed (containing 40% fat and 20% fructose), - purchased from Jiangsu Nantong Trofe Feed Technology Co., Ltd.; control feed - purchased from Nantong Trofe Feed Technology Co., Ltd.

[0054] experiment procedure:

[0055] The mice were randomly divided into two groups according to body weight, the control diet group (ND) and the high-fat and high-sugar diet group (HFHSD). After the mice were fed adaptively for 1 week, the control feed group was given the control feed, and the high-fat and high-sugar feed group was given the high-fat and high-sugar feed. During this period, the mice were weighed every week, and their body wei...

Embodiment 3

[0059] Protective effect of high expression of estrogen-related receptor α in liver on high-fat and high-sugar diet (HFHSD)-induced mouse NASH model

[0060] Animals: 40 male C57BL / 6J mice, SPF grade, 4 weeks old, purchased from Beijing Weitong Lihua. All animals were maintained on a 12-h alternating circadian rhythm with free access to food and drink.

[0061] Instruments: animal weight scales; slicers; automatic biochemical analyzers; microscopes

[0062]Reagent: AAV8-Esrra (adeno-associated virus AAV8 vector carrying mouse-derived Esrra gene, which can express ERRα protein in mouse liver) adeno-associated virus-purchased from Shanghai Hanheng Biotechnology Co., Ltd.; AAV8-control adeno-associated virus-purchased From Shanghai Hanheng Biological Technology Co., Ltd.; high-fat and high-sugar feed (containing 40% fat and 20% fructose),-purchased from Jiangsu Nantong Trophy Feed Technology Co., Ltd.; control feed-purchased from Nantong Trophy Feed Technology Co., Ltd. company...

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Abstract

The invention relates to an application of an encoding gene ESRRA of an estrogen-related receptor alpha (ERR alpha) in preparation of a medicine for preventing or treating liver diseases. The liver diseases include non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), alcoholic fatty liver disease (AFLD), hepatic fibrosis, or cirrhosis. The adeno-associated virus is utilized to construct an ERRalpha overexpression vector system, and the fact that the ERR alpha gene and a delivery system of the ERR alpha gene can be used for preventing or treating the liver diseases is proved on various disease models.

Description

technical field [0001] The present invention belongs to the field of gene function and application, and in particular relates to the application of an orphan nuclear receptor, that is, the encoding gene ESRRA of estrogen-related receptor α (Estrogen-related receptor α, ERRα) in the preparation of drugs for preventing or treating liver diseases . Background technique [0002] The protein estrogen-related receptor alpha (ERRα) encoded by the gene ESRRA is a class of orphan nuclear receptors. It can participate in the transcription process of many downstream signaling molecules and play an important role in regulating mitochondrial synthesis, oxidative metabolism and inflammatory response (Front. Endocrinol. 2019, 10: 206, doi: 10.3389 / fendo. 2019.00206). First, ERRα is a key transcription factor for mitochondrial synthesis and oxidative metabolism, and its downstream target genes and target proteins (including PGC1α, PDK4, and MCAD, etc.) are involved in mitochondrial synthes...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K48/00A61K38/17A61P1/16
CPCA61K48/005A61K38/1796A61P1/16A61K48/00A61K38/17
Inventor 孙宏斌戴量冯志奇刘慧
Owner CHINA PHARM UNIV
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