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CN-121971589-A - Meteorin protein or gene antithrombotic action

CN121971589ACN 121971589 ACN121971589 ACN 121971589ACN-121971589-A

Abstract

The invention relates to the fields of molecular biology and biological medicine, and in particular discloses Meteorin protein or gene antithrombotic effect. Experiments prove that after Meteorin protein is given for incubation, the platelet aggregation reaction can be obviously inhibited, the platelet spreading area is reduced, the blood clot contraction is delayed, and simultaneously, the ATP release, the alpha particle release and the activation of the surface integrin alpha IIb beta 3 of the platelets are inhibited. In the whole thrombus experiment, meteorin protein can effectively inhibit arterial thrombosis. As Meteorin protein is endogenous protein of human body, has small side effect, has higher safety as potential medicine and has good industrialization prospect.

Inventors

  • MIAO CHAOYU
  • MIAO ZHUWEI
  • CHEN CANXIN
  • ZHU XIAOYAN
  • Wu hanxiao
  • AN XIAOYU

Assignees

  • 中国人民解放军海军军医大学

Dates

Publication Date
20260505
Application Date
20250830

Claims (10)

  1. The use of Meteorin protein or gene and its potentiator for the preparation of an antithrombotic agent.
  2. 2. The use according to claim 1, wherein the potentiating agent is selected from the group consisting of agonists, upregulators and stabilizers.
  3. 3. The use according to claim 1, wherein the Meteorin protein has the amino acid sequence shown in SEQ ID No. 1.
  4. 4. The use according to claim 1, wherein the medicament further comprises a conventional pharmaceutically acceptable carrier.
  5. 5. The use according to claim 1, wherein the agent upregulates Meteorin protein expression.
  6. Use of a meteorin protein or gene and a potentiator thereof for the preparation of a reagent for inhibiting platelet aggregation in an ex vivo blood sample.
  7. 7. The use according to claim 6, wherein the ex vivo blood sample is a platelet suspension.
  8. Use of a meteorin protein or gene and a potentiator thereof for the preparation of an agent for inhibiting the shrinkage of a platelet clot in an ex vivo blood sample.
  9. 9. The use according to claim 8, wherein the ex vivo blood sample is a platelet suspension.
  10. 10. A method of screening for potential substances that are antithrombotic, comprising the steps of: a) Contacting the candidate substance with a system comprising Meteorin proteins or genes; b) Observing the effect of a candidate substance on Meteorin protein or gene expression and activity, wherein the candidate substance is an antithrombotic potential substance if the candidate substance is capable of promoting Meteorin gene expression or increasing Meteorin protein activity.

Description

Meteorin protein or gene antithrombotic action Technical Field The invention relates to the fields of molecular biology and biological medicine, in particular to Meteorin protein or gene antithrombotic effect. Background Meteorin (Metrn) is a nerve factor encoded by Metrn gene on human chromosome 16 and mouse chromosome 17, belonging to secreted proteins, consisting of 293 amino acids in total, with a molecular weight of about 31kDa. Structurally, 5 disulfide bonds are reported consisting of 10 conserved Cys residues. It was found to start in 2004 and be expressed mainly in the central nervous system, exerting neuroprotective effects. Thrombotic diseases are a serious class of cardiovascular and cerebrovascular diseases, such as ischemic stroke and myocardial infarction, and constitute a serious threat to human life health. For the diseases, the existing antiplatelet medicines such as aspirin, clopidogrel and the like are clinically used. However, maintaining the balance between the curative effect and the bleeding adverse reaction is always a key problem in the use process of the medicine. Thus, there is a need to develop new therapeutic targets to enhance antithrombotic efficacy without increasing bleeding risk. The prior art discloses Meteorin for a variety of purposes. For example, patent application number 2022109162665 discloses a shRNA lentiviral vector for knocking out Metrn genes and application, and specifically discloses that the shRNA lentiviral vector for knocking out Metrn genes has remarkable effects in promoting hematopoietic stem/progenitor cell mobilization and promoting proliferation and migration of bone marrow hematopoietic stem/progenitor cells. Patent publication number CN115948544B discloses application of CITED4 and/or METRN in differential diagnosis of disc degeneration degree, specifically discloses METRN showing significant differences in tissues of different disc degeneration degrees, has higher differential diagnosis value to disc degeneration degree, and can be used for differential diagnosis of disc degeneration. Patent application number 201810021543X discloses the use of nickel-striated proteins for the treatment of allodynia, hyperalgesia, spontaneous pain and phantom pain. Meteorin as a novel secreted protein, no study report on thrombotic diseases is found. Disclosure of Invention The first object of the invention is to provide pharmaceutical uses of Meteorin proteins or genes and their potentiators. A second object of the present invention is to provide the use of Meteorin proteins or genes and their potentiators in the preparation of in vitro inhibiting agents. It is a third object of the present invention to provide a method of screening for potential substances that are antithrombotic. In order to achieve the first object, the invention adopts the following technical scheme: meteorin protein or gene and the application of a synergist thereof are used for preparing antithrombotic medicines. In the pharmaceutical use as described above, further, the potentiating agent is selected from the group consisting of an agonist, an up-regulator and a stabilizer. In the pharmaceutical application, the amino acid sequence of Meteorin protein is shown as SEQ ID NO. 1. In the pharmaceutical use as described above, further, the medicament may further comprise a conventional pharmaceutical carrier, and be prepared into various dosage forms in the form of pharmaceutical compositions. For example, it can be made into conventional solid preparation medicine such as tablet, powder or capsule, etc., and can be made into injection when used for injection. In the pharmaceutical use as described above, further, the agent upregulates Meteorin protein expression. In order to achieve the second purpose, the invention adopts the following technical scheme: Meteorin protein or gene and the use of its synergist for preparing reagent for inhibiting platelet aggregation or platelet clot contraction of blood sample. In the use of an in vitro inhibiting agent as described above, further, the ex vivo blood sample is referred to as a platelet suspension. The reagent for inhibiting platelet aggregation or platelet clot contraction in the isolated blood sample has the direct function of keeping the blood sample stable in an in-vitro environment and avoiding platelet activation or aggregation, so Meteorin protein or gene and a synergist thereof can be used as an additive of a blood sample collection tube. The in vitro inhibition reagent has a certain scientific research value in a scientific research laboratory and has a good commercial value in clinic, inspection and drug research and development. In the fields of clinical examination and in-vitro diagnosis, the in-vitro inhibition reagent can be used for preserving and detecting blood samples, and can avoid the advanced activation of platelets in the processes of collection and detection, thereby ensuring the accuracy of clinical detection data such as p