Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin 300052, China.
Department of Nephrology, Tianjin Medical University No.2 Hospital, Tianjin 300211, China.
Int Immunopharmacol. 2018 Nov;64:386-393. doi: 10.1016/j.intimp.2018.09.027. Epub 2018 Sep 22.
Primary biliary cholangitis (PBC) is an autoimmune liver disease characterised by destruction of small intrahepatic bile ducts. Recent studies suggest that miRNAs play a critical role in the pathogenesis of liver diseases. However the role served by miRNAs in the pathogenesis of PBC is still not clear.
The differentially expressed genes and miRNAs were identified by bioinformatics analysis. Gene ontology and KEGG pathway analyses were conducted to explore the function of the differentially expressed genes. miRNA target genes were predicted using miRecords. The differentially expressed genes and miRNAs were validated by qRT-PCR in PBC patients along with healthy controls and chronic hepatitis B patients as control. Flow cytometric analysis was conducted to identify the Th17 and Treg cells frequency.
15 differentially expressed miRNAs and 1897 mRNAs were identified from the profile. miR-181a was validated as the differentially expressed miRNA. BCL-2 and CDKN1B were predicted as the target gene of miR-181a and validated differentially expressed in PBC patients. However, only BCL-2 was negative correlated with miR-181a. The Th17 cells frequency was increased in PBC patients while the Treg cells frequency was decreased. Moreover, the expression of BCL-2 was positive correlated with Th17 cells frequency.
Down-regulated miR-181a in CD4+ T cells may decrease apoptosis of Th17 cells via up-regulated BCL-2 in the pathogenesis of PBC.
原发性胆汁性胆管炎（PBC）是一种自身免疫性肝病，其特征是小的肝内胆管破坏。最近的研究表明，miRNA 在肝脏疾病的发病机制中起着关键作用。然而，miRNA 在 PBC 发病机制中的作用尚不清楚。
通过生物信息学分析鉴定差异表达的基因和 miRNA。通过 GO 和 KEGG 通路分析探讨差异表达基因的功能。使用 miRecords 预测 miRNA 靶基因。通过 qRT-PCR 在 PBC 患者以及健康对照和慢性乙型肝炎患者中验证差异表达的基因和 miRNA。通过流式细胞术分析鉴定 Th17 和 Treg 细胞频率。
从该谱中鉴定出 15 个差异表达的 miRNA 和 1897 个 mRNAs。miR-181a 被验证为差异表达的 miRNA。BCL-2 和 CDKN1B 被预测为 miR-181a 的靶基因，并在 PBC 患者中验证为差异表达。然而，只有 BCL-2 与 miR-181a 呈负相关。PBC 患者的 Th17 细胞频率增加，而 Treg 细胞频率降低。此外，BCL-2 的表达与 Th17 细胞频率呈正相关。
CD4+T 细胞中下调的 miR-181a 可能通过上调 BCL-2 来减少 Th17 细胞的凋亡，从而导致 PBC 的发生。
