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Use of sFRP2 and PCPE1 as joint target points in preparation of medicament for fibrotic diseases

A technology for fibrotic diseases and drugs, used in drug combinations, respiratory diseases, biological tests, etc., can solve the problem of unclear interaction of procollagen, and achieve the effect of inhibiting collagen deposition

Inactive Publication Date: 2019-10-22
RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, whether sFRP2 and PCPE1 interact and have synergistic effects on the processing of procollagen remains unclear

Method used

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  • Use of sFRP2 and PCPE1 as joint target points in preparation of medicament for fibrotic diseases
  • Use of sFRP2 and PCPE1 as joint target points in preparation of medicament for fibrotic diseases
  • Use of sFRP2 and PCPE1 as joint target points in preparation of medicament for fibrotic diseases

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Experimental program
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Embodiment 1

[0022] 1. Experimental method

[0023] ① Shear analysis of type Ⅰ procollagen in vitro

[0024] (1) Extraction of radioactive 3H-type procollagen refers to published literature [Scott IC, Blitz IL, Pappano WN, et al. Mammalian BMP-1 / Tolloid-related metalloproteinases, including novel family member mammalian Tolloid-like 2, have differential enzymatic activities and distributions of expression relevant to patterning and skeleton [J]. Dev Biol, 1999, 213(2): 283-300.]. Mix the purified protein 3H-type I procollagen and BMP1, then add 20ng PCPE1, 20ng sFRP2 or 10ng PCPE1 / 10ng sFRP2 respectively, incubate in 100μl buffer A at 37°C for 6h;

[0025] (2) Add SDS sample lysate, heat in a 95°C metal bath for 5 minutes to denature the protein, and then place it on ice to cool for 5 minutes;

[0026] (3) The protein sample was separated by 7.5% SDS-PAGE gel, and then transferred to the membrane;

[0027] (4) Add EN3HANCE (PerkinElmer) and use autoradiography to detect uncut type I pro...

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Abstract

The present invention relates to the use of sFRP2 and PCPE1 as joint target points in the preparation of a medicament for fibrotic diseases. It is demonstrated by experiments that sFRP2 and PCPE1 havedirect interactions in vitro and in vivo, and that the blockade of the sFRP2 and PCPE1 interaction inhibits collagen deposition. Therefore, blocking the interaction of the sFRP2 and PCPE1 is expectedto provide potential target points for the treatment of diseases associated with abnormal fibrotic formation, such as the preparation of the medicament for fibrotic diseases.

Description

technical field [0001] The invention belongs to the field of drugs for fibrotic diseases, and particularly relates to the application of sFRP2 and PCPE1 as combined targets in the preparation of drugs for fibrotic diseases. Background technique [0002] The extracellular matrix plays an important role in maintaining life. Studies have shown that the specific molecular structure of the extracellular matrix determines the microenvironment and functions of cells, such as cell differentiation or metabolic state. Many studies have confirmed that collagen gene mutations or defects involved in collagen synthesis can lead to many diseases, such as osteogenesis imperfecta, achondroplasia and Ehlers-Danlos syndrome. In addition, when the synthesis rate of collagen exceeds the degradation rate, collagen deposition increases, which may lead to fibrotic diseases, such as pulmonary fibrosis, liver cirrhosis, and cardiovascular fibrosis. [0003] BMP1 was originally recognized as a member...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/68A61K45/00A61P11/00
CPCG01N33/6803A61K45/00A61P11/00G01N2333/46
Inventor 黄国瑞周丽斌王晓郭薇
Owner RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE