Migita Kiyoshi, Komori Atsumasa, Kozuru Hideko, Jiuchi Yuka, Nakamura Minoru, Yasunami Michio, Furukawa Hiroshi, Abiru Seigo, Yamasaki Kazumi, Nagaoka Shinya, Hashimoto Satoru, Bekki Shigemune, Kamitsukasa Hiroshi, Nakamura Yoko, Ohta Hajime, Shimada Masaaki, Takahashi Hironao, Mita Eiji, Hijioka Taizo, Yamashita Haruhiro, Kouno Hiroshi, Nakamuta Makoto, Ario Keisuke, Muro Toyokichi, Sakai Hironori, Sugi Kazuhiro, Nishimura Hideo, Yoshizawa Kaname, Sato Takeaki, Naganuma Atsushi, Komatsu Tatsuji, Oohara Yukio, Makita Fujio, Tomizawa Minoru, Yatsuhashi Hiroshi
NHO-AIH study group, Nagasaki Medical Center, kubara 2-1001-1 Omura, Nagasaki, 856-8562, Japan.
Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1 Sakamoto, Nagasaki, Japan.
PLoS One. 2015 Nov 17;10(11):e0136908. doi: 10.1371/journal.pone.0136908. eCollection 2015.
Recent studies have demonstrated that micro (mi)RNA molecules can be detected in the circulation and can serve as potential biomarkers of various diseases. This study used microarray analysis to identify aberrantly expressed circulating miRNAs in patients with type 1 autoimmune hepatitis (AIH) compared with healthy controls. Patients with well-documented and untreated AIH were selected from the National Hospital Organization (NHO)-AIH-liver-network database. They underwent blood sampling and liver biopsy with inflammation grading and fibrosis staging before receiving treatment. To further confirm the microarray data, circulating expression levels of miR-21 and miR-122 were quantified by real-time quantitative polymerase chain reaction in 46 AIH patients, 40 patients with chronic hepatitis C (CHC), and 13 healthy controls. Consistent with the microarray data, serum levels of miR-21 were significantly elevated in AIH patients compared with CHC patients and healthy controls. miR-21 and miR-122 serum levels correlated with alanine aminotransferase levels. Circulating levels of miR-21 and miR-122 were significantly reduced in AIH patients with liver cirrhosis, and were inversely correlated with increased stages of fibrosis. By contrast, levels of circulating miR-21 showed a significant correlation with the histological grades of inflammation in AIH. We postulate that aberrantly expressed serum miRNAs are potential biomarkers of AIH and could be implicated in AIH pathogenesis. Alternations of miR-21 and miR-122 serum levels could reflect their putative roles in the mediation of inflammatory processes in AIH.
近期研究表明，微小（mi）RNA分子可在循环系统中被检测到，并且可作为多种疾病的潜在生物标志物。本研究采用微阵列分析，以识别1型自身免疫性肝炎（AIH）患者与健康对照相比异常表达的循环miRNA。从国立医院组织（NHO）-AIH-肝脏网络数据库中选取记录完整且未经治疗的AIH患者。他们在接受治疗前进行了血液采样和肝活检，并进行炎症分级和纤维化分期。为进一步确认微阵列数据，采用实时定量聚合酶链反应对46例AIH患者、40例慢性丙型肝炎（CHC）患者和13例健康对照者的miR-21和miR-122循环表达水平进行定量。与微阵列数据一致，与CHC患者和健康对照相比，AIH患者血清miR-21水平显著升高。miR-21和miR-122血清水平与丙氨酸氨基转移酶水平相关。肝硬化AIH患者的miR-21和miR-122循环水平显著降低，且与纤维化分期增加呈负相关。相比之下，循环miR-21水平与AIH炎症组织学分级显著相关。我们推测，异常表达的血清miRNA是AIH的潜在生物标志物，可能参与AIH的发病机制。miR-21和miR-122血清水平的变化可能反映了它们在AIH炎症过程介导中的假定作用。
