Functional role of PPAR-γ on the proliferation and migration of fibroblast-like synoviocytes in rheumatoid arthritis.

Functional role of PPAR-γ on the proliferation and migration of fibroblast-like synoviocytes in rheumatoid arthritis.
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DOI:
10.1038/s41598-017-12570-6
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发表时间:
2017-10-04
期刊:
影响因子:
4.6
通讯作者:
Li J
Li J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Li XF;Sun YY;Bao J;Chen X;Li YH;Yang Y;Zhang L;Huang C;Wu BM;Meng XM;Li J

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过氧化物酶体增殖物激活受体γ参与了多种疾病的正常生理过程和病理过程。本研究旨在探讨PPAR-γ在类风湿关节炎(RA)成纤维细胞样滑膜细胞(FLSS)增殖和迁移中的作用及其机制。在本研究中,我们发现PPAR-γ在RA滑膜中的表达显著低于OA和正常人,在佐剂性关节炎(AA)中也有低表达。此外,T0070907(12.5 μM)或PPAR-γsiRNA抑制PPAR-FLSS的表达,除TIPM-1外,均能促进其增殖和c-Myc、Cyclin D1、MMP1、MMP9表达。这些数据表明,PPAR-γ的上调可能在RA FLSS中发挥关键作用。有趣的是,PIODITazone(25 μM)和超表达载体与pEGFP-N1-PPAR-γ共孵育后,除TIMP-1外,FLSS的增殖和c-Myc、Cyclin D1、MMP1和MMP9的表达均降低。进一步研究表明,PPAR-γ可能诱导激活Wnt/β-catenin信号转导。总之,这些结果表明,PPAR-γ可能在FLSS激活和激活Wnt/β-Catenin信号通路中起着关键作用。
Peroxisome proliferator-activated receptor (PPAR)-γ is involved in both normal physiological processes and pathology of various diseases. The purpose of this study was to explore the function and underlying mechanisms of PPAR-γ in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) proliferation and migration. In the present study, we found PPAR-γ expression was remarkably reduced in RA synovium patient compare with OA and normal, as well as it was low-expression in Adjuvant-induced arthritis (AA). Moreover, inhibition PPAR-γ expression by T0070907 (12.5 μM) or PPAR-γ siRNA could promote FLSs proliferation and expressions of c-Myc, Cyclin D1, MMP-1, and MMP-9 in AA FLSs, except for TIPM-1. These date indicate that up-regulation of PPAR-γ may play a critical role in RA FLSs. Interestingly, co-incubation FLSs with Pioditazone (25 μM) and over expression vector with pEGFP-N1-PPAR-γ reduced proliferation and expressions of c-Myc, Cyclin D1, MMP-1, and MMP-9 in AA FLSs, besides TIMP-1. Further study indicates that PPAR-γ may induce activation Wnt/β-catenin signaling. In short, these results indicate that PPAR-γ may play a pivotal role during FLSs activation and activation of Wnt/β-catenin signaling pathway.
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