Inhibition of smoothened decreases proliferation of synoviocytes in rheumatoid arthritis
Inhibition of smoothened decreases proliferation of synoviocytes in rheumatoid arthritis
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DOI：
10.1038/cmi.2015.67
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发表时间：
2017-02-01
影响因子：
24.1
通讯作者：
Zheng, Song Guo
中科院分区：
文献类型：
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作者：
Zhu, Shang-ling;Huang, Jian-lin;Zheng, Song Guo
成纤维细胞样滑膜细胞（FLS）有助于类风湿关节炎（RA）的滑膜增生。Smoothened（Smo）是音刺猬（Shh）信号传导的关键成分，有助于肿瘤细胞增殖。本研究的目的是探讨Smo在RA滑膜细胞增殖中的作用。从RA滑膜中分离FLS。使用Smo拮抗剂（GDC-0449）和靶向FLS中Smo基因的小干扰RNA（siRNA）研究Shh信号传导。采用kit-8法检测细胞增殖情况，流式细胞仪检测细胞周期分布和凋亡情况。实时荧光定量PCR和Western blot检测细胞周期相关基因和蛋白。与对照组相比，用GDC-0449或Smo-siRNA处理的FLS显示出显著降低的增殖（P
Fibroblast-like synoviocytes (FLSs) contribute to synovial hyperplasia in rheumatoid arthritis (RA). Smoothened (Smo) is a key component of sonic hedgehog (Shh) signaling and contributes to tumor cell proliferation. The objective of this study was to investigate the role of Smo in RA synoviocyte proliferation. FLSs were isolated from RA synovium. Shh signaling was studied using a Smo antagonist (GDC-0449) and small interfering RNA (siRNA) targeting the Smo gene in FLSs. Cell proliferation was quantified by using kit-8 assay and cell cycle distribution and apoptosis were evaluated by flow cytometry. Cell cycle-related genes and proteins were detected by real-time PCR and western blot. FLSs treated with GDC-0449 or Smo-siRNA showed significantly decreased proliferation compared to controls (P