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Application of extracellular matrix protein 1 and regulator thereof in preparing medicament for diagnosing or treating allergic diseases

A technology for exogenous matrix and allergic asthma, applied in allergic diseases, gene therapy, drug combination, etc., can solve the problem of few specific treatment methods

Active Publication Date: 2014-06-04
CENT FOR EXCELLENCE IN MOLECULAR CELL SCI CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Although the research on Th2 cell-mediated allergic diseases is deepening at home and abroad, there are relatively few effective and specific treatments, a large part of which is due to the diversity and complexity of allergens

Method used

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  • Application of extracellular matrix protein 1 and regulator thereof in preparing medicament for diagnosing or treating allergic diseases
  • Application of extracellular matrix protein 1 and regulator thereof in preparing medicament for diagnosing or treating allergic diseases
  • Application of extracellular matrix protein 1 and regulator thereof in preparing medicament for diagnosing or treating allergic diseases

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Experimental program
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Effect test

Embodiment approach

[0079] As an embodiment of the present invention, the ECM1 inhibitor is an antibody that specifically binds to ECM1. Said antibody can be a monoclonal antibody or a polyclonal antibody. ECM1 protein can be used to immunize animals, such as rabbits, mice, rats, etc. to produce polyclonal antibodies; various adjuvants can be used to enhance the immune response, including but not limited to Freund's adjuvant. Similarly, cells expressing ECM1 or antigenic fragments thereof can be used to immunize animals to produce antibodies. The antibody can also be a monoclonal antibody, which can be prepared using hybridoma technology (see Kohler et al., Nature 256; 495, 1975; Kohler et al., Eur.J.Immunol.6:511, 1976; Kohler et al., Eur. J. Immunol. 6:292, 1976; Hammerling et al., In Monoclonal Antibodies and T Cell Hybridomas, Elsevier, N.Y., 1981).

[0080] As an embodiment of the present invention, the ECM1 inhibitor is an antibody or ligand that specifically binds to an upstream protein ...

Embodiment 1

[0155] Example 1. ECM1 is specifically highly expressed in type II helper T cells (Th2)

[0156] The present inventors isolated naive CD4+ helper T cells from C57BL / 6 mice, cultured and differentiated them under Th1 or Th2 conditions, and harvested the cells within 1 to 5 days for Real-time PCR ( figure 1 a) and Western blot ( figure 1 b) The expression of ECM1 was detected, and it was found that ECM1 was specifically and highly expressed in Th2 cells, and reached a peak on the 4th and 5th day.

[0157] The inventors also detected five different subtypes of Th cells, and found that ECM1 was specifically highly expressed only in type II helper T cells (Th2) (real-time PCR ( figure 1 c), Western blot ( figure 1 d) and supernatant ELISA ( figure 1 e)).

[0158] The detection of other immune cells found that ECM1 was only slightly expressed in dendritic cells, and there was almost no expression in B cells and CD8+ T cells ( figure 1 f).

Embodiment 2

[0159] Example 2, ECM1 is upregulated by the classic Th2 signaling pathway

[0160] In Th2 cells, when the STAT6 molecule was knocked out (KO), the expression of ECM1 also disappeared ( figure 2 a).

[0161] If the retrovirus system is transferred to the persistently expressed STAT6 (STAT6-CA), ECM1 ( figure 2 b).

[0162] When the inventors used RNAi technology to down-regulate GATA3, the expression of ECM1 was also down-regulated ( figure 2 c).

[0163] In order to prove whether GATA3 can directly bind to the promoter of ECM1, a CHIP experiment was carried out. The results proved that GATA3 can directly bind to the four GATA-box sequences -1381~-1327, -940~-935, -708~-703, -42~-37 at the 5' end of ECM1 (the sequence position is based on ECM1, GenBank accession number Upstream of the start codon of AAI45382.1), especially the -1381~-1327 sequence is the most obvious ( figure 2 d).

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Abstract

The invention relates to application of extracellular matrix protein 1 (ECM1) and a regulating agent thereof in preparing a medicament for diagnosing or treating allergic diseases. The invention firstly discloses that the ECM1 can regulate migration of Th2 cells, and is closely related to occurrence or development of Th2 cell mediated allergic diseases, so that the ECM1 can be used as a medicinal target to develop a medicament for preventing or treating allergic diseases.

Description

technical field [0001] The invention belongs to the field of biotechnology; more specifically, the invention relates to the application of extracellular matrix protein 1 and its regulator in the preparation of drugs for the diagnosis or treatment of allergic diseases. Background technique [0002] In the past two decades, the incidence of allergic diseases such as asthma has exceeded 25% of the population in Western countries, and it has shown a steady upward trend. In China's developed cities such as Beijing, Shanghai and Guangzhou, the incidence of allergic diseases is also increasing year by year. This not only affects people's quality of life, especially children's asthma, which directly affects the normal development of children's bodies, but also hinders the development of the country's economy. [0003] When the naive Th cells in the body are activated by antigen-presenting cells, they undergo clonal proliferation and cell differentiation to form different cell subty...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K45/00A61K48/00A61K31/7088A61K39/395G01N33/68A61P37/08A61P33/14A61P17/00A61P11/06
Inventor 孙兵李振虎张渊吴晓东
Owner CENT FOR EXCELLENCE IN MOLECULAR CELL SCI CHINESE ACAD OF SCI
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