Taurine Reduced Epidural Fibrosis in Rat Models after Laminectomy via Downregulating EGR1
Taurine Reduced Epidural Fibrosis in Rat Models after Laminectomy via Downregulating EGR1
复制标题
牛磺酸通过下调 EGR1 减少椎板切除术后大鼠模型的硬膜外纤维化
DOI：
10.1159/000445581
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发表时间：
2016-01-01
影响因子：
--
通讯作者：
Ge, Yingbin
中科院分区：
文献类型：
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作者：
Yang, Lei;Tang, Jian;Ge, Yingbin
背景/目标：硬膜外纤维化是椎板切除术后的常见并发症，已被证明与手术效果差密切相关。既往研究表明，牛磺酸对肺纤维化和肝纤维化具有显著的抗纤维化作用。本研究旨在观察牛磺酸对椎板切除术后硬膜外纤维化大鼠的影响，并探讨其可能的分子机制。方法：采用椎板切除术建立大鼠硬膜外纤维化模型。牛磺酸治疗后，采用Masson三色染色和免疫组化染色观察硬膜外纤维化。使用细胞计数试剂盒-8测定法测定细胞活力。Annexin V/Propidium Iodide双染法检测成纤维细胞凋亡。采用基因芯片技术检测基因表达谱的变化。通过qRT-PCR测量mRNA表达。进行慢病毒感染以建立稳定的敲低和过表达细胞系。通过Western blot检测纤维化相关蛋白的表达。结果：牛磺酸治疗显着减少椎板切除术诱导的硬膜外纤维化大鼠模型。然而，牛磺酸的这种作用不依赖于TGF-13/Smad通路，其证据是TGF-β及其受体的表达没有变化。此外，牛磺酸对细胞凋亡几乎没有影响。有趣的是，牛磺酸处理显着降低了体内和体外纤维化增强剂EGFR 1（早期生长反应蛋白1）的表达。此外，EGR 1的过表达增加了成纤维细胞的活化，而EGR 1敲低则达到了相反的效果，表明EGR 1在牛磺酸对TGF-β诱导的纤维化的抑制作用中起着关键作用。结论：牛磺酸治疗后，减少硬膜外纤维化在体内和体外成纤维细胞的活化减少介导的EGFR 1。牛磺酸有望成为预防椎板切除术后硬膜外纤维化的潜在药物。(C)2016作者由S Karger AG，巴塞尔出版
Background/Aims: Epidural fibrosis, a common complication after laminectomy, has been demonstrated to be closely associated with poor surgical outcomes. Previous studies showed that taurine had remarkable anti-fibrotic effects on lung and liver fibrosis. We performed this study to investigate the effects of taurine in rat models of epidural fibrosis after laminectomy and to explore the potential molecular mechanism. Methods: Laminectomy was performed on each rat to establish epidural fibrosis model. After taurine treatment, Masson's trichrome and immunohistochemistry staining were used to examine epidural fibrosis. Cell viability was determined using the Cell Counting Kit-8 assay. Annexin V/Propidium Iodide double staining was performed to detect fibroblasts apoptosis. Microarray was adopted to identify significantly changed mRNAs. mRNA expression was measured by qRT-PCR. Lentivirus infection was performed to establish stable knockdown and overexpression cell lines. The expression of fibrosis-related proteins was determined via Western blot. Results: Taurine treatment markedly reduced laminectomy-induced epidural fibrosis in rat models. However, this effect of taurine was independent on TGF-13/Smad pathway, evidenced by no change in the expression of TGF-beta and its receptors. Besides, taurine had almost no effect on cell apoptosis. Interestingly, taurine treatment significantly decreased expression of EGR1 (Early growth response protein 1), an enhancer of fibrosis, both in vivo and in vitro. Furthermore, overexpression of EGR1 increased activation of fibroblasts, while EGR1 knockdown achieved an opposite effect, indicating that EGR1 plays a key role in the inhibitory effect of taurine on TGF-beta-induced fibrosis. Conclusions: Reduced epidural fibrosis in vivo and decreased activation of fibroblasts in vitro after taurine treatment was mediated by EGR1. Taurine promises to be a potential prevention for epidural fibrosis after laminectomy. (C) 2016 The Author(s) Published by S Karger AG, Basel