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An agent comprising fgf2 as an effective ingredient for treatment or prevention of asthma and chronic obstructive pulmonary disease

A chronic obstructive, active ingredient technology, applied in the prevention and treatment of asthma and chronic obstructive pulmonary disease agents, COPD and Th1 asthma mouse models, can solve the problems of pathogenesis limitation, COPD pathogenesis has not been elucidated, etc.

Active Publication Date: 2007-04-25
MD HEALTHCARE INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, the use of the Th1 / Th2 hypothesis emphasizing the importance of promoting Th2 immune responses to explain the pathogenesis of asthma is limited
[0016] At the same time, the pathogenesis of COPD involved in asthma has not been elucidated

Method used

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  • An agent comprising fgf2 as an effective ingredient for treatment or prevention of asthma and chronic obstructive pulmonary disease
  • An agent comprising fgf2 as an effective ingredient for treatment or prevention of asthma and chronic obstructive pulmonary disease
  • An agent comprising fgf2 as an effective ingredient for treatment or prevention of asthma and chronic obstructive pulmonary disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0127] Example 1 Asthma induced by IL-13 overexpression and the correlation between TGF-β1 and VEGF

[0128] In order to study the pathogenesis of IL-13-induced asthma, IL-13 transgenic mice were prepared, and the AHR of each mouse was measured. The effect of IL-13 overexpression on the expression of TGF-β1 and VEGF was also investigated.

[0129] 1-1 Preparation of IL-13 transgenic mice

[0130] By conventional methods (Zhou Zhu et al., J.Clin.Invest., 103:779-788, 1999; Tang et al., J.Clin.Invest., 98:2845-2853, 1996; Ray et al., J.Clin. Invest., 100:2501-2511, 1997) to generate IL-13 transgenic mice. To enable selective expression of IL-13 candidate genes in the airways, constructs containing IL-13 candidate genes were linked to promoters (B. Stripp and J. Whitsett, University of Cincinnati), using the inducible 10kDa Clara cell protein (CC10 ) expression promoter. To generate inducible transgenic mice in which expression of the embedded gene can be regulated from th...

Embodiment 2

[0140] Example 2 The role of FGF2 in the pathogenesis of IL-13-induced asthma

[0141] To investigate the role of FGF2 in the pathogenesis of IL-13-induced asthma and the role of downstream regulators TGF-β1 and VEGF, AHR and airway remodeling in FGF2 knockout (- / -) mice were observed.

[0142] 2-1 AHR induced by FGF2 deficiency

[0143]The following experiments were performed to investigate the link between FGF2 and AHR. FGF2 knockout mice were purchased from Jackson Lab (CA, USA). Using similar procedures as described in Examples 1-2 and Examples 1-3, the AHR (DRS) to methacholine and the concentrations of VEGF and TGF-β1 in BAL were studied, demonstrating that AHR and VEGF and TGF-β1 concentration increased (Figure 5 and Figure 6). Fig. 5 is a graph showing the expression levels of VEGF and TGF-β1 obtained from FGF2 knockout mice and wild-type controls in BAL. Figure 6 is a graph showing FGF2 knockout mice treated with VEGF blockers as described in Examples 1-4 and ...

Embodiment 3

[0152] The development of asthma caused by embodiment 3TGF-β1

[0153] In order to study the pathogenesis of asthma mediated by IL-13-induced TGF-β1 expression, TGF-β1 transgenic mice were prepared using a procedure similar to that described in Example 1-1, and the following experiments were performed.

[0154] 3-1 Airway remodeling induced by TGF-β1

[0155] AHR resulting from airway remodeling was studied using a procedure similar to that described in Examples 1-2 above (Fig. 7). Figure 7 is a graph showing the comparison of AHR over time between TGF-β1 transgenic mice and wild type controls. Figure 8 is a graph showing a comparison of AHR versus methacholine over time between TGF-β1 transgenic mice and wild type controls.

[0156] As shown in Figure 7, TGF-β1 induced severe airway resistance, a conclusion supported by Penh's results. However, as shown in Figure 8, AHR was inhibited by methacholine. This result suggests that overexpression of TGF-β1 is only involved ...

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Abstract

The present invention relates an agent comprising FGF2(Fibroblast Growth Factor-2 or basic Fibroblast Growth Factor(bFGF)) as an effective ingredient for treatment or prevention of Asthma and Chronic Obstructive Pulmonary Disease(COPD). Also, The present invention relates Th1 asthma and COPD mouse animal model induced by Ovalbumin and double strand RNA. The therapeutic agent comprising FGF2 of the present invention can be used for treatment or prevention for airway fibrosis, airway inflammation, airway hyperresponsiveness, airway remodeling, asthma and COPD. Also, Th1 asthma and COPD mice animal model induced by Ovalbumin and double strand RNA can be used for development of therapeutic agent for asthma and COPD.

Description

technical field [0001] The present invention relates to an agent for preventing and treating asthma and chronic obstructive pulmonary disease (COPD) containing FGF2 (fibroblast growth factor-2, or basic fibroblast growth factor, bFGF) as an active ingredient. The present invention also relates to mouse models of COPD and Th1 asthma induced by ovalbumin (OA) and double-stranded RNA (dsRNA). Background technique [0002] The prevalence of asthma has nearly doubled over the past 20 years, and asthma today affects 8-10% of the world's population. Asthma is a chronic inflammatory disorder of the airways characterized by airway hyperresponsiveness (AHR) to nonspecific stimuli and airway remodeling in association with elements involved such as fibroblasts and myofibroblasts Associated with changes in cellular structure and function. Asthma is roughly divided into bronchial asthma and cardiac asthma, but usually asthma refers to simple bronchial asthma. [0003] Along with asthma...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/18
CPCC07K14/57A01K2227/105A61K38/1825A01K2217/203C12N15/8509A01K2267/0368A01K2217/07C07K14/5437A01K2207/10A01K2207/05C07K14/52A01K67/0275A61P11/00A61P11/06A61P11/08A61P43/00A61K38/18
Inventor 金润根姜寿亨金炳文孙美苑
Owner MD HEALTHCARE INC
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