Department of Pharmacy, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital of Wannan Medical College), Wuhu, Anhui Province, China; The Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, Anhui Province Key Laboratory of Major Autoimmune Diseases, School of Pharmacy, Institute for Liver Disease of Anhui Medical University, Hefei, Anhui Province, China.
The Key Laboratory of Anti-inflammatory and Immune Medicines, Ministry of Education, Anhui Province Key Laboratory of Major Autoimmune Diseases, School of Pharmacy, Institute for Liver Disease of Anhui Medical University, Hefei, Anhui Province, China.
Int Immunopharmacol. 2020 Dec;89(Pt A):107067. doi: 10.1016/j.intimp.2020.107067. Epub 2020 Oct 8.
There are multiple causes of liver fibrosis, common ones include ethanol, toxins, and cholestasis. However, whether these different etiologies lead to the same pathological outcomes contain common genetic targets or signaling pathways, the current research has not attracted widespread attention. GSE40041 and GSE55747 were downloaded from the Gene Expression Omnibus (GEO) database. GSE40041 and GSE55747 represent the differential expression profiles in the liver of mice with bile duct ligation (BDL) and carbon tetrachloride (CCl4) induced liver fibrosis models, respectively. By using GEO2R, 701 differential expression genes (DEGs) in GSE40041 and 6540 DEGs in GSE55747 were identified. 260 co-DEGs were shared and extracted for gene ontology (GO) analysis. Through GO analysis, it was found that the regulation of cell migration in biological processes (BPs) was closely related to the pathogenesis of liver fibrosis, and the genes involved in this process include a key gene, chemokine (C-X-C motif) ligand 14 (CXCL14). Subsequently, further bioinformatic analysis showed that CXCL14 may be regulated by miR-122 to participate in the progression of liver fibrosis. Then real-time PCR and western blotting were performed to validate the expression of CXCL14 in liver tissue after liver fibrosis caused by different etiologies (ethanol, CCl4). The expression of CXCL4 in liver fibrosis induced by BDL was verified in another GEO dataset. Basically consistent with our bioinformatics results, our experimental results showed that the expression of CXCL14 was most significantly increased in alcoholic liver fibrosis model, followed by CCl4-induced liver fibrosis, which was also significantly increased in the BDL-induced model. Thus, CXCL14 can act as a common potential genetic target for different liver fibrosis diseases.
存在多种导致肝纤维化的原因，常见的有乙醇、毒素和胆汁淤积。然而，这些不同的病因是否导致相同的病理结果包含共同的遗传靶点或信号通路，目前的研究尚未引起广泛关注。从基因表达综合数据库（GEO）中下载了 GSE40041 和 GSE55747。GSE40041 和 GSE55747 分别代表胆管结扎（BDL）和四氯化碳（CCl4）诱导的肝纤维化模型中小鼠肝脏的差异表达谱。通过使用 GEO2R，在 GSE40041 中鉴定到 701 个差异表达基因（DEG），在 GSE55747 中鉴定到 6540 个 DEG。共提取了 260 个共同 DEG 进行基因本体（GO）分析。通过 GO 分析，发现生物过程（BP）中细胞迁移的调节与肝纤维化的发病机制密切相关，涉及该过程的基因包括关键基因趋化因子（C-X-C 基序）配体 14（CXCL14）。随后，进一步的生物信息学分析表明，CXCL14 可能受 miR-122 调控，参与肝纤维化的进展。然后，通过实时 PCR 和 Western blot 验证了不同病因（乙醇、CCl4）引起肝纤维化后肝组织中 CXCL14 的表达。在另一个 GEO 数据集验证了 BDL 诱导的肝纤维化中 CXCL4 的表达。与我们的生物信息学结果基本一致，我们的实验结果表明，CXCL14 在乙醇性肝纤维化模型中的表达增加最为显著，其次是 CCl4 诱导的肝纤维化，BDL 诱导的模型中也显著增加。因此，CXCL14 可以作为不同肝纤维化疾病的共同潜在遗传靶点。
