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Novel application of inhibitor for protein HSD17B13 or coding genes thereof

A technology that encodes genes and inhibitors, applied in the field of biomedicine, can solve problems such as the lack of effective treatments

Active Publication Date: 2014-01-22
JIANGSU MEIDISEN BIOLOGICAL MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Commonly used drugs are mainly aimed at lowering blood lipids and protecting liver cells, and there is a lack of effective treatments that directly act on liver lipid deposition

Method used

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  • Novel application of inhibitor for protein HSD17B13 or coding genes thereof
  • Novel application of inhibitor for protein HSD17B13 or coding genes thereof
  • Novel application of inhibitor for protein HSD17B13 or coding genes thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0065] Example 1. Differential proteomics research on lipid droplet-associated proteins between normal people and fatty liver patients

[0066] In this embodiment, the isolated liver tissue samples come from: normal people and fatty liver patients. Among them, the liver tissue samples of normal people come from healthy volunteers (without liver disease or other diseases); the liver tissue samples of fatty liver patients come from patients with clinically diagnosed fatty liver, provided by Peking University First Hospital.

[0067] 1. Liver lipid droplet purification

[0068] 1. Soak the liver tissue sample in precooled 4°C PBS, carefully remove the capsule and connective tissue with small scissors, cut into 1mm×1mm×1mm small pieces, and transfer to 10ml precooled hypotonic solution A.

[0069] Pre-cooled hypotonic solution A: 20mM glycine, 250mM sucrose, pH7.8, prepared with double distilled water. Each concentration is the final concentration of the corresponding component...

Embodiment 2、I

[0110] Example 2, Detection of HSD17B13 Protein Expression in Liver Tissues of Type II Diabetic Mice and High Fat Mice

[0111] In order to further confirm that there is a positive relationship between HSD17B13 protein expression and lipid deposition in liver tissue, the inventors of the present invention investigated the lipid deposition in liver tissue of type II diabetic mice and high-fat mice showing clinical symptoms of fatty liver. The situation and the expression level of HSD17B13 protein were detected.

[0112] 1. Expression detection of HSD17B13 protein in liver tissue of type II diabetic mice

[0113] Type II diabetic mice (db / db): the genetic background is C57BL / KsJ, purchased from Shanghai Southern Model Organism Research Center. The mice exhibited clinical symptoms of fatty liver.

[0114] Control mice (db / m): the genetic background is C57BL / KsJ, purchased from Shanghai Southern Model Organism Research Center. The mice had no clinical symptoms of fatty liver. ...

Embodiment 3

[0135] Example 3, Construction of recombinant adenovirus expressing HSD17B13 protein

[0136] In this example, AdEasy system will be used to package recombinant adenovirus expressing HSD17B13 protein, as follows:

[0137] 1. Preparation of HSD17B13 recombinant adenovirus (Ad-HSD17B13)

[0138] 1. Cloning of the full-length sequence of HSD17B13

[0139] The amino acid sequence of the HSD17B13 protein is shown in Sequence 1 of the Sequence Listing, and its coding sequence is shown in the 25th-927th nucleotides from the 5' end of the Sequence 2 of the Sequence Listing. Analyze the HSD17B13 gene shown in Sequence 2, design primers near both sides of its coding region, and add a His tag to the downstream primers. The final primer sequence is as follows:

[0140] Upstream primer: 5'-GC ATGAACATCCATCCTAGAAATCC-3' (positions 3-24 of this sequence are positions 25-46 of sequence 2);

[0141] Downstream primer: 5’-GC TCA ATGGTGATGGTGATGATG TTTCATTTTTGATTTTGT -3' (underlined is the ...

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Abstract

The invention discloses a novel application of an inhibitor for protein HSD17B13 or coding genes thereof. The novel application provided by the invention particularly means the application of the inhibitor for the protein HSD17B13 or the coding genes thereof in preparation of products for preventing and / or treating fatty liver. Proved by experiments, through immunizing a C57 wild-type mouse by using a recombinant adenovirus carrying an HSD17B13 gene, the condition that the liver of the mouse is subjected to obvious fatty change can be observed, oil red of a slice of the liver is stained and shows the accumulation of a lot of fat, and the content of triglyceride and cholesterol in liver tissues is increased remarkably, so that the HSD17B13 possibly participates in the formation process of fatty liver. The novel application has an important significance in prevention and / or treatment of fatty liver.

Description

technical field [0001] The invention belongs to the field of biomedicine, and relates to a new application of an inhibitor of HSD17B13 protein or its coding gene, in particular to the application of the inhibitor of HSD17B13 protein or its coding gene in the preparation of products for preventing and / or treating fatty liver. Background technique [0002] HSD17B13 is a steroid dehydrogenase that belongs to the 17β-HSD family and was cloned in 2007. The human HSD17B13 gene is located on chromosome 4q22, contains seven exons, and encodes a protein of 300 amino acids. 17β-HSD belongs to a subfamily of SDR, and SDR is a very large family involved in a series of physiological and pathophysiological processes such as reproduction, development, and obesity in mammals. There are 14 members in the 17β-HSD subfamily. Other members are mainly involved in the activation and inactivation of sex hormones. Their abnormalities are closely related to reproductive tumors such as prostate canc...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61P1/16A61K48/00A61K38/44A61K39/395
Inventor 管又飞苏文
Owner JIANGSU MEIDISEN BIOLOGICAL MEDICINE
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