Monoclonal antibody of follistatin-like protein l and application thereof

A monoclonal antibody, follistatin technology, applied in the fields of application, antibody, anti-animal/human immunoglobulin, etc., can solve the problem that no one has disclosed anti-FSTL1 antibody to inhibit pulmonary fibrosis, and achieve the effect of great application prospects

Inactive Publication Date: 2014-12-24
NANKAI UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There have been recent reports about FSTL1 promoting the role of TGF-β in pulmonary fibrotic

Method used

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  • Monoclonal antibody of follistatin-like protein l and application thereof
  • Monoclonal antibody of follistatin-like protein l and application thereof
  • Monoclonal antibody of follistatin-like protein l and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] Example 1.Fstl1 is highly expressed in the lung tissue of IPF patients and in the mouse pulmonary fibrosis model induced by bleomycin

[0056] In order to determine whether the expression of Fstl1 is abnormal in idiopathic pulmonary fibrosis, first, using the gene analysis data of IPF patient and normal human lung tissue published by Pardo et al. in 2005, the analysis found that compared with normal lung tissue, in IPF The expression of FSLT1mRNA in the patient's lung tissue increased by 2.4 times ( figure 1 Middle A).

[0057] Using real-time quantitative PCR analysis of human lung tissue from Beijing Chaoyang Hospital, it was further confirmed that the expression of FSTL1 mRNA in the lung tissue of IPF patients was significantly higher than that in normal lung tissue (1.7 times, Pfigure 1 B); while in IPF patient lung fibroblasts, FSTL1mRNA expression level is 2.3 times of normal lung fibroblasts ( figure 1 C).

[0058] In addition, the role of FSTL1 was further inv...

Embodiment 2

[0062] Example 2. Pulmonary fibrosis symptoms induced by bleomycin in haplo-knockout Fstl1 heterozygous mice were significantly alleviated

[0063] In order to further study the biological significance of the induced expression of Fstl1 in the process of pulmonary fibrosis, a model of pulmonary fibrosis induced by bleomycin in Fstl1 genetically engineered mice was established. Homozygous mice due to Fstl1 gene knockout (Fstl1 - / - mice) died of respiratory distress after birth, and Fstl1 gene knockout heterozygous mice (Fstl1 + / - mice) were used to study bleomycin-induced pulmonary fibrosis. First, compared with wild-type mice, Fstl1 + / - The expression of FSTL1 protein in mouse lung tissue was significantly reduced, and the increased FSTL1 protein induced by bleomycin was expressed in Fstl1 + / - It was also significantly reduced in mouse lung tissue ( figure 2 A).

[0064] Fstl1 + / - Mice have strong tolerance to bleomycin-induced lung injury. After 21 days of high-dose bl...

Embodiment 3

[0070] Example 3. Fstl1 deletion does not affect the pulmonary inflammatory response caused by bleomycin treatment

[0071] In the bleomycin injury model, persistent inflammatory response often promotes the progression of fibrosis, but the role of inflammation in pulmonary fibrosis is still controversial. Since Fstl1 regulates inflammatory responses in rheumatoid arthritis and cardiac allografts, Fstl1 + / - Inflammatory responses in mice versus wild-type mice following bleomycin treatment. Inflammatory cells detected in bronchoalveolar lavage (BAL) fluid after 7 days of bleomycin treatment revealed Fstl1 + / - The total number of inflammatory cells and the number of various types of inflammatory cells (including macrophages, neutrophils and lymphocytes) in the lung tissue of mice and wild-type mice were increased, but there was no difference (Table 2, image 3 A).

[0072] Likewise, FACS analysis indicated that Fstl1 + / - Lymphocyte subsets (such as CD4 + , CD8 + , NKT, NK a...

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PUM

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Abstract

The invention relates to a function of follistatin-like protein l (FSTL1) for promoting the process of pulmonary fibrosis disease in vivo, and use of an anti-FSTL1 antibody in treatment, alleviation or improvement of the pulmonary fibrosis disease or symptom.

Description

technical field [0001] The present invention relates to a monoclonal antibody and its application, in particular to a monoclonal antibody for neutralizing follistatin-like protein 1 and its application in regulating tissue fibrosis. Background technique [0002] The essence of visceral fibrosis is the repair response after tissue damage to protect the relative integrity of tissues and organs. Fibrosis can occur in a variety of organs. The main pathological changes are the increase of fibrous connective tissue and the decrease of parenchymal cells in organ tissues. Although the proliferated fibrous connective tissue repairs the defect, it does not have the structure and function of the original parenchymal cells of the organ. Sustained progression of fibrosis can lead to organ structural damage, functional decline, and even failure, seriously threatening human health and life. According to the statistics of relevant agencies of the US government, 45% to 55% of the patients w...

Claims

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Application Information

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IPC IPC(8): C12N5/20C12N15/13C12N15/63C07K16/18A61K39/395A61P11/00C12R1/91
Inventor 宁文董莺莺李霄鹤李莲
Owner NANKAI UNIV
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