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Application of gsdmd protein and its target in the preparation of drugs for treating inflammatory bowel disease

An inflammatory and drug technology, applied in the application field of GSDMD protein and its target in the preparation of drugs for the treatment of inflammatory bowel disease, can solve problems such as unclear, anti-enteritis mechanism research, etc.

Active Publication Date: 2022-05-27
NANJING MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The research on the mechanism of anti-intestinal inflammation against GSDMD is not yet clear

Method used

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  • Application of gsdmd protein and its target in the preparation of drugs for treating inflammatory bowel disease
  • Application of gsdmd protein and its target in the preparation of drugs for treating inflammatory bowel disease
  • Application of gsdmd protein and its target in the preparation of drugs for treating inflammatory bowel disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Example 1: GSDMD is expressed in both intestinal epithelium and lamina propria

[0047] 1.1 Experimental method

[0048] Mice were sacrificed, colon tissue samples were collected, the feces of the mouse colon were washed with sterile PBS, and a section was cut, rolled into a Swiss roll, fixed with 4% paraformaldehyde, embedded, and sliced.

[0049] 1.2 Experimental results

[0050] The localized expression of immunofluorescent marker GSDMD (red and green) in the mouse gut, E-cadherin (green) and CX3CR1 (red) represent intestinal epithelial and lamina propria immune cells, respectively. see the results figure 1 , showing that GSDMD, E-cadherin and CX3CR1 all co-localize.

Embodiment 2

[0051] Example 2: Activated expression of GSDMD protein in intestinal tissue of DSS enteritis mice

[0052] 2.1 Experimental method

[0053] Day 0: DSS was dissolved in sterile water to make a 2.5% DSS solution, and then wild mice (WT) and GSDMD knockout mice were allowed to drink continuously for 6 days.

[0054] Day 6: Change the 2.5% DSS solution to normal drinking water.

[0055] On the ninth day: the mice were sacrificed, colon tissue samples were collected, the feces of the mouse colon were washed with sterile PBS, and a section of weighing record was intercepted. Protein lysis buffer was added and the protein was collected.

[0056] 2.2 Experimental results

[0057] Anti-mouse GSDMD antibody and anti-mouse β-actin antibody were used in the protein lysate of section 2.1 to detect the activation of GSDMD by western. The western results showed that the expression and activation of GSDMD were significantly increased in DSS-induced colitis mice. See figure 2 (lanes 1 a...

Embodiment 3

[0058] Example 3: DSS enteritis model study shows that GSDMD has a protective effect in the process of enteritis

[0059] 3.1 Experimental method

[0060] Day 0: DSS was dissolved in sterile water to make a 2.5% DSS solution, and then wild mice (WT) and GSDMD knockout mice were allowed to drink continuously for 6 days.

[0061] Day 6: Change the 2.5% DSS solution to normal drinking water.

[0062] The ninth day: the mice were sacrificed, colon tissue samples were collected, the feces of the mouse colon were washed with sterile PBS, and the length of the colon was measured and photographed.

[0063] 3.2 Experimental results, during the mouse modeling period, the mice were weighed every day, and the body weight time curve was made, see image 3 Part A (black line is WT mouse, red line is GSDMD knockout mouse), see the length of colon tissue in mice image 3 The middle part B (the left of the figure is WT mouse, the right of the figure is GSDMD knockout mouse). The results sh...

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Abstract

The invention discloses the application of a GSDMD protein and its target in the preparation of medicines for treating inflammatory bowel disease. The invention discloses the application of GSDMD protein in screening or preparing medicine or kit for treating intestinal diseases. The invention also discloses the application of the GSDMD target cGAS protein in drug screening and the application of its inhibitor. The invention provides the anti-inflammatory effect of GSDMD in the occurrence of enteritis, can provide treatment ideas and theoretical basis for various GSDMD-related inflammatory diseases, and provide new targets and new ideas for screening and preparing drugs for treating inflammatory bowel diseases.

Description

technical field [0001] The present invention relates to the application of GSDMD protein and its target in preparing medicine for treating inflammatory bowel disease. Background technique [0002] Inflammatory Bowel Disease (IBD) mainly includes ulcerative colitis (UC) and Crohn's disease (CD). UC is characterized by diffuse inflammation, mainly involving the mucosal surface and submucosa of the colon and rectum, with recurrent episodes; CD may involve the entire digestive tract or any part of the digestive tract from the oral cavity to the perianal region. The manifestations are different, but both are diseases mediated by the environment and genes and mediated by the immune system, and the intestinal mucosal immune abnormality is the main pathological inducement. IBD patients will have clinical symptoms such as abdominal pain, vomiting, diarrhea, and rectal bleeding, which bring great pain to the patient's work and life. The disease currently lacks effective cure methods ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K38/17A61K45/00A61P1/00A61P1/04
CPCA61K38/1709A61K45/00A61P1/00A61P1/04
Inventor 杨硕王冰微马春梅刘雪
Owner NANJING MEDICAL UNIV
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