Application of GSDMD protein and target thereof in preparation of medicines for treating inflammatory bowel diseases

An inflammatory bowel disease and inflammatory 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 ambiguity and research on the mechanism of anti-inflammation

Active Publication Date: 2020-08-14
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 target thereof in preparation of medicines for treating inflammatory bowel diseases
  • Application of GSDMD protein and target thereof in preparation of medicines for treating inflammatory bowel diseases
  • Application of GSDMD protein and target thereof in preparation of medicines for treating inflammatory bowel diseases

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] The mice were sacrificed, the colonic tissue samples were collected, the colonic feces of the mice were washed clean with sterile PBS, and a section was cut out, rolled into a Swiss roll, fixed with 4% paraformaldehyde, embedded, and sectioned.

[0049]1.2 Experimental results

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

Embodiment 2

[0051] Example 2: Activation and expression of GSDMD protein in intestinal tissues of mice with DSS enteritis

[0052] 2.1 Experimental method

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

[0054] Day 6: Replace the 2.5% DSS solution with normal drinking water.

[0055] Ninth day: the mice were killed, colon tissue samples were collected, the feces in the colon of the mice were washed with sterile PBS, and a weighing record was taken. Add protein lysate and collect protein.

[0056] 2.2 Experimental results

[0057] Use anti-mouse GSDMD antibody and anti-mouse β-actin antibody for the protein lysate in part 2.1, and detect the activation of GSDMD by western. The western results show that the expression and activation of GSDMD are significantly increased in DSS-induced colitis mice. See figure 2 (Swimming lanes 1 and 2 are control groups, and swi...

Embodiment 3

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

[0059] 3.1 Experimental method

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

[0061] Day 6: Replace the 2.5% DSS solution with normal drinking water.

[0062] Ninth day: the mice were sacrificed, colon tissue samples were collected, the feces in the colon of the mice were washed with sterile PBS, 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 In part A (the black line is WT mice, the red line is GSDMD knockout mice), the length of mouse colon tissue is shown in image 3 Part B in the middle (the left side of the figure is the WT mouse, and the right side of the figure ...

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Abstract

The invention discloses an application of GSDMD protein and a target thereof in preparation of medicines for treating inflammatory bowel diseases. The invention discloses application of the GSDMD protein in screening or preparation of the medicines or kits for treating intestinal diseases. The invention further discloses application of the GSDMD target cGAS protein in medicine screening and application of an inhibitor of the GSDMD target cGAS protein. The invention provides an anti-inflammatory effect of the GSDMD in enteritis, can provide a treatment thought and a theoretical basis for various GSDMD-related inflammatory diseases, and provides a new target and a new thought for screening and preparing the medicines for treating inflammatory bowel diseases.

Description

technical field [0001] The invention relates to the application of GSDMD protein and its target in the preparation of medicine for treating inflammatory bowel disease. Background technique [0002] Inflammatory bowel disease (Inflammatory Bowel Disease, IBD) mainly includes ulcerative colitis (Ulcerative colitis, UC) and Crohn's disease (Crohn's disease, CD). UC is characterized by diffuse inflammation, mainly involving the superficial and submucosa of the colon and rectum, with recurrent attacks; CD may involve the entire digestive tract or any part of the digestive tract from the oral cavity to the perianal area, although the two are different in etiology and clinical The manifestations are different, but both are diseases mediated by the environment and genes and mediated by the immune system, and abnormal intestinal mucosal immunity is the main pathological cause. IBD patients will have clinical symptoms such as abdominal pain, vomiting, diarrhea, and rectal bleeding, w...

Claims

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Application Information

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