Inhibitory effect of paeoniflorin on rat fibroblast-like synoviocytes hyperplasia induced by PGE2 via β-arrestin 2 regulating EP2 receptor

Q4 Pharmacology, Toxicology and Pharmaceutics

中国药理学通报 Pub Date : 2012-01-01 DOI:10.3969/J.ISSN.1001-1978.2012.011

Qingtong Wang, Yu Ma, B. Huang, Wei Wei

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引用次数: 1

Abstract

Aim To investigate the potential molecular mechanism of paeoniflorin(Pae) in inhibiting PGE2 induced rat fibroblast-like synoviocytes(FLSs) hyperplasy.Methods Rat FLSs were cultured in the presence of prostaglandin E2(PGE2) with or without different concentrations of Pae.FLSs proliferations were determined by 3H-TdR incorporation assay.Cyclic adenosine monophosphate(cAMP) levels in synoviocytes were assessed by radioimmunoassay(RIA).The expressions of EP2 and β-arrestin 2 in whole FLSs or on membrane were measured by Western blot or flow cytometry.Results Pae significantly inhibited rat FLS proliferation induced by PGE2 via increasing cAMP levels.High levels of total EP2,β-arrestin 2 and membrane β-arrestin 2 expression in FLSs induced by PGE2 were decreased by different concentrations of Pae administration.EP2 was downregulated on FLSs membrane after PGE2 stimulation;however,was restored by Pae in various degrees.Conclusions Our findings suggest that Pae inhibits rat FLSs proliferation induced by PGE2 via arresting EP2 receptor internalization by inhibiting β-arrestin 2 recruit to cell membrane.

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芍药苷通过β-阻滞蛋白2调控EP2受体对PGE2诱导的大鼠成纤维细胞样滑膜细胞增生的抑制作用

目的探讨芍药苷(Pae)抑制PGE2诱导大鼠成纤维细胞样滑膜细胞(FLSs)增生的可能分子机制。方法在前列腺素E2(PGE2)和不同浓度Pae的作用下培养大鼠FLSs。用3H-TdR掺入法检测FLSs的增殖情况。采用放射免疫法(RIA)测定滑膜细胞内环腺苷单磷酸(cAMP)水平。采用Western blot和流式细胞术检测EP2和β-阻滞蛋白2在整个FLSs和膜上的表达。结果Pae通过提高cAMP水平显著抑制PGE2诱导的大鼠FLS增殖。不同浓度的Pae均可降低PGE2诱导的fls中EP2、β-阻滞蛋白2和膜β-阻滞蛋白2的高水平表达。PGE2刺激后FLSs膜上EP2表达下调，Pae则不同程度恢复。结论Pae通过抑制β-阻滞蛋白2向细胞膜募集，抑制EP2受体内化，从而抑制PGE2诱导的大鼠FLSs增殖。

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来源期刊

中国药理学通报 Pharmacology, Toxicology and Pharmaceutics-Pharmacology

CiteScore

0.80

自引率

0.00%

发文量

11201

期刊介绍： Chinese Pharmacological Bulletin (CPB) is an academic monthly magazine sponsored by the Chinese Association for Science and Technology, the Chinese Pharmacological Society, and Anhui Medical University. Publicly issued domestically and internationally, CN:34:1086/R,ISSN:1001-1978。 The inclusion status of Chinese Pharmaceutical Bulletin (CPB): 1. This journal has been identified as a core medical journal by the China Science Citation Database (CSCD) of the Document Information Center of the Chinese Academy of Sciences (since 1993, there are 909 journals in the core library); 2. Selected as a pharmaceutical core journal by the editor in chief of Peking University Library's "Overview of Chinese Core Journals" (Peking University Core), 1st to 8th editions (1243 scientific and technological journals, including 232 medical and health journals); 3. Designated by the Institute of Science and Technology Information of the Ministry of Science and Technology of China as a source journal for Chinese scientific and technological paper statistics (China Science and Technology Core Journal); 4. Other: Domestic: Chinese Academic Journal Abstracts, Chinese Basic Medical Abstracts, Chinese Pharmaceutical Abstracts, Chinese Biological Abstracts, Chinese Academic Journals (CD version), Wanfang Database, VIP Database, etc; International: Chemical Abstract (USA), Corrective Bulletin on Science and Technology, CBST (Japan), Biological Abstract (USA), Biochemical Abstract (USA), EMBASE/Excerpta Medica (Netherlands), Index Copernicus (Poland), Kunst and Wissen (Germany), WPRIM (World Health Organization Western Pacific Regional Medical Index), Scopus (Netherlands, 2019 CiteScore 0.9), A&I (Netherlands), Centre for Agriculture and Biosciences international (CAB international, UK), Biosis Previews (USA), etc.