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Cyr61 synthesis is induced by Interleukin-6 and promotes migration and invasion of fibroblast-like synoviocytes in Rheumatoid arthritis

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Alternative Title
류마티스 관절염 활막세포에서 인터루킨 6에 의한 Cyr61 발현 및 세포 이동과 침투 증가에 관한 연구
Abstract
Interleukin-6 (IL-6) is involved in fibroblast-like synoviocyte (FLS) activation and promotes pannus formation and bone and cartilage destruction in rheumatoid arthritis(RA). Cysteine-rich 61 (Cyr61) protein regulates cell proliferation, migration, and differentiation. The aim of this study was to investigate the role of Cyr61 in RA-FLS migration and invasion after IL-6 stimulation. In results, Cyr61 levels were elevated in FLSs from RA patients compared to those in osteoarthritis patients. Control and IL-6-treated FLSs showed differential gene expression. IL-6 stimulated protein synthesis of Cyr61, which was attenuated by the extracellular signal-related kinase 1/2 (ERK 1/2) inhibitor, PD98059, and knockdown of early growth response 3 (EGR3), but not of JUN.IL-6-induced Cyr61 protein synthesis increased expression of MMP2. Cyr61 promoted FLS migration and invasion in an autocrine manner. Knockdown of CYR61 and a neutralizing antibody attenuated Cyr61 synthesis and IL-6 induced FLS migration. Thus, by modulating the ERK/EGR3 pathway, IL-6 stimulated Cyr61 production and in turn increased invasiveness of FLS. Our data suggest that Cyr61 might be a potential target to prevent the progression of joint damage in RA.
Author(s)
최창민
Issued Date
2023
Awarded Date
2023-02
Type
Dissertation
URI
https://dcoll.jejunu.ac.kr/common/orgView/000000010760
Alternative Author(s)
Chang Min Choi
Affiliation
제주대학교 의학전문대학원
Department
의학전문대학원 의학과 복합학위과정
Advisor
김진석, 조문제
Table Of Contents
1. INTRODUCTION 1
2. MATERIALS AND METHODS 3
3. RESULTS 9
1. Cyr61 expression is upregulated in the FLSs of RA patients induced by IL-6. 9
2. Regulation by IL-6 of expression of genes associated with migration and mitogen-activated protein kinase (MAPK) response. 15
3. IL-6-induced Cyr61 production depends on ERK 1/2,EGR3 pathway. 22
4. IL-6 induced increase in autocrine Cyr61 protein production from FLSs. 31
5. IL-6 stimulated RA-FLS migration and invasion through Cyr61 protein secretion. 40
4. DISCUSSION 50
5. REFERENCE 54
6. 국문 초록 57
Degree
Doctor
Publisher
제주대학교 의학전문대학원
Citation
최창민. (2023). Cyr61 synthesis is induced by Interleukin-6 and promotes migration and invasion of fibroblast-like synoviocytes in Rheumatoid arthritis.
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School of Medicine > School of Medicine MD-phD Course
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