| 房志强,阮 柏,刘晶晶,许 皓,王 琳.肝血窦内皮细胞介导的他莫昔芬对非酒精性脂肪性肝炎治疗作用的转录组学分析[J].,2022,(9):1609-1613 |
| 肝血窦内皮细胞介导的他莫昔芬对非酒精性脂肪性肝炎治疗作用的转录组学分析 |
| Transcriptome Analysis of the LSECs-mediated Therapeutic Effect of Tamoxifen on Nonalcoholic Steatohepatitis |
| 投稿时间：2021-09-28 修订日期：2021-10-23 |
| DOI：10.13241/j.cnki.pmb.2022.09.002 |
| 中文关键词: 他莫昔芬 非酒精性脂肪性肝炎 肝血窦内皮细胞 |
| 英文关键词: Tamoxifen Nonalcoholic steatohepatitis Liver sinusoidal endothelial cells |
| 基金项目:国家重点研究发展计划项目（2016YFA0102100） |
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| 中文摘要: |
| 摘要 目的：探究他莫昔芬对饮食诱导的非酒精性脂肪性肝炎小鼠肝血窦内皮细胞的代谢、炎症及纤维化等通路基因表达的影响。方法：采用8周龄的雄性C57BL/6小鼠，给予MCD饲料喂养6周后，每天腹腔注射一次他莫昔芬（100 mg/kg），持续5天。分离并收集肝血窦内皮细胞，加入1 mL TRIzol试剂吹打至沉淀消失，放入-80℃冰箱保存。样本后续送至基迪奥生物公司进行转录组测序并在Omicsmart平台进行生物信息学分析。部分生物信息学分析数据来自已经发表的文献并通过Omicshare分析平台分析。结果：转录组测序发现，差异基因KEGG和GO分析发现差异基因在免疫和炎症通路富集。通过分析肝脏内皮特异性代谢基因表达，我们发现他莫昔芬治疗逆转了NASH过程中部分代谢基因的下调，以及NASH过程中CCL2、CXCL2、CXCL5和VCAM-1等促炎基因和Col1a1、Col1a2、Col3a1、Tgfb2、和Timp1等促纤维化基因的表达上调。同时，GSEA分析也显示他莫昔芬抑制了炎症和纤维化通路的表达。结论：他莫昔芬可能通过逆转非酒精性脂肪性肝炎对小鼠肝血窦内皮细胞代谢基因的改变以及炎症及纤维化相关基因的上调来治疗非酒精性脂肪性肝炎。 |
| 英文摘要: |
| ABSTRACT Objective: To determine the effect of tamoxifen on the metabolism, inflammation and fibrosis-related gene expression of LSECs in a diet-induced NASH mouse model. Methods: 8-week-old male C57BL/6 mice were purchased from Charles River. Then these mice were fed MCD diets for 6 weeks and administrated tamoxifen intraperitoneally (100 mg/kg/day) for five consecutive days. The next day, these mice were anesthetized and LSECs were isolated and suspended by 1 ml TRIzol Reagent and placed at -80℃ refrigerator. The samples were then sent to Genedenovo Biotechnology for RNA sequencing and subsequent bioinformatic analysis were performed on Omicsmart platform. We also reanalyzed others' sequencing data to support our evidence using Omicshare tools. Results: Through analyzing our own RNA-seq data and reanalyzing Xiong X's RAN-seq data, combined with liver ECs-specific metabolic gene sets derived from Joanna Kalucka et al, we found that compared to normal LSECs, inflammation and fibrosis-related gene expression was upregulated notably. These effects were abolished by tamoxifen administration. Meanwhile, GSEA analysis suggested that tamoxifen downregulated the expression of inflammation and fibrosis-related pathway. Conclusion: Tamoxifen reversed the alterations of metabolic genes of LSECs and up-regulated genes related to inflammation and fibrosis in mice with nonalcoholic steatohepatitis. |
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