Application of LINC01503 serving as therapeutic target to preparation of medicines for treatment of pediatric asthma

A technology for childhood asthma and therapeutic targets, applied in the field of biomedicine

Pending Publication Date: 2020-02-28
CHILDRENS HOSPITAL OF FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

According to different activation pathways, macrophages can be divided into classically activated M1 type and alternatively activated M2 type. The state of macrophages can directly affect the occu

Method used

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  • Application of LINC01503 serving as therapeutic target to preparation of medicines for treatment of pediatric asthma
  • Application of LINC01503 serving as therapeutic target to preparation of medicines for treatment of pediatric asthma
  • Application of LINC01503 serving as therapeutic target to preparation of medicines for treatment of pediatric asthma

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Example 1 LINC01503 is significantly highly expressed in asthmatic patients

[0029] We first detected the expression of LINC01503 in PBMCs from asthmatic patients and normal controls. We collected peripheral blood samples from 46 healthy persons and 28 asthmatic patients. The average age of asthma patients was 6.12±2.42 years old; the ratio of male to female was 19 / 9; the average number of eosinophils in peripheral blood was 425.77±248.73 (unit·μL -1, normal value 60-300), the total positive rate of IgE was 50.00%; the percentage of cases with increased airway resistance was 74%. The mononuclear cells in the peripheral blood of healthy subjects and asthma patients were collected by density gradient centrifugation, and the expression of LINC01503 was detected by RT-qPCR. The results showed that compared with healthy subjects, the expression of LINC01503 in asthmatic patients was significantly increased [(1.63±0.10) vs (1.01±0.04), Pfigure 1 A). In asthmatic patients,...

Embodiment 2

[0030] Example 2 Expression of LINC01503 in Different Activation Processes of Macrophages

[0031] In an inflammatory state, peripheral blood monocytes travel to the lungs to transform into macrophages [ 10 ] . Macrophages are the most numerous immune cells in the respiratory tract. Under the stimulation of different environmental factors, they will move in different directions, accompanied by dynamic changes in the expression of a series of genes, thus exerting different regulatory effects on diseases [ 8 ] . In order to explore whether the expression of LINC01503 changes in different processes of macrophages, we used LPS 200ng / ml and IL-4 20ng / ml to induce macrophages to M1 and M2 respectively, and detected the expression of LINC01503 by RT-qPCR. We found that the expression of LINC01503 was downregulated in LPS-stimulated macrophages ( figure 2 A). In contrast, LINC01503 expression was gradually upregulated in IL-4-stimulated macrophages ( figure 2 B). The a...

Embodiment 3

[0032] Example 3 LINC01503 promotes the activation of M1 macrophages and inhibits the activation of M2 macrophages

[0033] In order to further explore the role of LINC01503 in macrophage activation, we knocked down LINC01503 by liposome transfection of siRNA, and detected the effect of knockdown of LINC01503 on macrophage activation by RT-qPCR. siRNA can effectively reduce the expression of LINC01503, and the knockdown efficiency is more than 80% ( image 3 A). After knocking down LINC01503, we found that the expressions of M2 macrophage marker genes CD206 and CD209 were significantly upregulated ( image 3 B,C), while the expression of marker genes IL-6, TNF-α, CXCL10 in M1 macrophages was significantly decreased ( image 3 D, E, F). The above results indicate that LINC01503 can promote the activation of M1 macrophages and inhibit the activation of M2 macrophages.

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Abstract

The invention discloses application of LINC01503 serving as therapeutic target to preparation of medicines for treatment of pediatric asthma. According to comparison between LINC01503 and a normal control, expression of LINC01503 in asthma patients is increased remarkably; LINC01503 in M1 macrophage is evidently down-regulated while LINC01503 in M2 macrophage is evidently up-regulated. According to siRNA knock-down experiments, LINC01503 promotes activation of M1 macrophage and realizes expression up-regulation of M1 marker genes such as IL-6, TNF-alpha and CXCL10; LINC01503 inhibits activation of M2 macrophage and realizes expression down-regulation of M2 marker genes such as CD206 and CD209. By Western blot, the fact that LINC01503 has influences on macrophage activation mainly through promotion of EPK phosphorylation, so that pediatric asthma can be effectively treated by inhibition of LINC01503 and downstream signal routing thereof.

Description

technical field [0001] The invention belongs to the field of biomedicine and relates to the application of LINC01503 as a therapeutic target in the preparation of medicaments for treating children's asthma. Background technique [0002] Bronchial asthma (referred to as asthma) is one of the most common chronic diseases of the respiratory tract in children, mainly manifested as chronic airway inflammation and airway hyperresponsiveness [ 1 ] . Asthma is an inflammatory disease caused by a combination of genetic, environmental and epigenetic factors [ 2 , 3 ] . Epidemiological studies have shown that the incidence of asthma has been rising rapidly in recent years [ 4 ] , but the DNA sequence is unlikely to undergo drastic changes in a short period of time, so changes in epigenetic factors may play a greater role in it. Epigenetic regulation including DNA methylation, histone modification and non-coding RNA, etc. [ 5 ] . [0003] Long non-coding RNA (l...

Claims

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Application Information

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IPC IPC(8): C12Q1/6883A61K45/00A61P11/06
CPCC12Q1/6883A61K45/00A61P11/06C12Q2600/158C12Q2600/178
Inventor 周玉峰夏莉
Owner CHILDRENS HOSPITAL OF FUDAN UNIV
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