Hyaluronic acid-curcumin conjugate suppresses the fibrotic functions of myofibroblasts from contractive joint by the PTGER2 demethylation.
Hyaluronic acid-curcumin conjugate suppresses the fibrotic functions of myofibroblasts from contractive joint by the PTGER2 demethylation.
复制标题
透明质酸-姜黄素缀合物通过 PTGER2 去甲基化抑制收缩关节肌成纤维细胞的纤维化功能。
DOI：
10.1093/rb/rbz016
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Wang Yunbing
中科院分区：
文献类型：
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作者：
Yu Dongjie;Zhuang Ze;Ren Jianhua;Hu Xuefeng;Wang Zhe;Zhang Jieyu;Luo Yuansen;Wang Kun;He Ronghan;Wang Yunbing
关节挛缩是关节制动和创伤后引起的一种以关节囊内肌成纤维细胞过度增殖为特征的纤维化并发症。关节挛缩的治疗效果不理想，患者常出现关节功能障碍。我们前期的研究表明，姜黄素在体外能够抑制肌成纤维细胞的增殖，但主要的挑战是姜黄素的水溶性和生物活性较低。在这项研究中，透明质酸-姜黄素（HA-Cur）共轭物的合成抑制肌纤维母细胞在关节挛缩。从关节挛缩患者的关节囊中分离细胞，并通过转化生长因子-β（TGF-β）诱导为活性肌成纤维细胞。采用免疫组化、逆转录-定量聚合酶链反应（PCR）、甲基化特异性PCR、western blot、transwell迁移实验和增殖实验研究HA-Cur的抗肝纤维化作用及其机制。结果表明，30 μM HA-Cur通过调节前列腺素E受体2（PTGER 2）甲基化和抑制TGF-β信号通路，显著减轻体外培养的关节肌成纤维细胞的纤维化功能。这可能为关节挛缩的治疗提供了一种机制，并为关节挛缩发病过程中的治疗提供了分子靶点PTGER 2。
Joint contracture is a fibrotic complication induced by joint immobilization and trauma, which is characterized as excessive myofibroblast proliferation in joint capsule. The treatments of joint contracture are unsatisfied and patients are suffered from joint dysfunction. Our previous study has shown that curcumin can inhibit myofibroblast proliferationin vitro, but the major challenge is the low aqueous solubility and biological activity of curcumin. In this study, hyaluronic acid-curcumin (HA-Cur) conjugate was synthesized to suppress myofibroblasts in joint contracture. Cells were isolated from the joint capsules of joint contracture patients and induced to active myofibroblasts by transforming growth factor-β (TGF-β). The anti-fibrotic function and mechanisms of HA-Cur were investigated by immunohistochemistry, reverse transcription-quantitative polymerase chain reaction (PCR), methylation-specific PCR, western blot, transwell migration assay and proliferation assay. Results showed that 30 μM HA-Cur significantly attenuated the fibrotic functions of myofibroblast in joint contracturein vitroby regulating the methylation of prostaglandin E receptor 2 (PTGER2) and inhibiting TGF-β signaling. This may provide a mechanism for the treatment of joint contracture, and provide a molecular target PTGER2 for therapy during the pathogenesis of joint contracture.