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浙江大學鑒定刀豆蛋白A誘發的暴肝早期miRNA表達譜

作者:admin 來源:聯川生物 發布時間: 2014-08-02 08:35  瀏覽次數:
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 浙大鑒定刀豆蛋白A誘發的暴肝早期miRNA表達譜

暴發性肝炎是一種嚴重的肝臟疾病,表現出大量肝細胞壞死,伴隨著肝功能衰竭的臨床癥狀。無論是病毒性和自身免疫性肝炎,巨噬細胞和T細胞的活化是肝損傷和暴發性肝臟疾病的發病過程中關鍵的初始步驟,然而其內在的分子機制尚不明確。越來越多的研究表明,micrornA(miRNA)在人類疾病發生發展中發揮重要的調控作用。

浙江大學朱海紅副研究員領銜的團隊對刀豆蛋白A(Con A)誘發肝炎的早期階段中的miRNA表達譜進行了深入分析,研究成果發表在7月刊的Cellular Physiology and Biochemisrty上。

研究人員分Balb/c小鼠注射刀豆注射劑,誘發暴發性肝炎,然后利用微陣列芯片對其肝組織中的miRNA表達譜進行分析(miRNA芯片項目由聯川生物承擔完成)。研究發現11種miRNAs在暴發性肝炎的早期肝組織與正常對照組肝組織之間存在顯著差異表達。其中,Mmu-miR-133a的差異表達最明顯,且具有最強的調控能力,可以調節47個mRNAs。Mmu-miR-10a在miRNA-GO-網絡中表達水平最高,同樣具有很強的調控能力。miR-133a和miR-10a的表達譜可被RT-PCR所驗證。

此研究結果表明,在早期階段,ConA誘發的暴發性肝炎誘導明顯差異的miRNA表達譜。該差異的miRNA表達譜可以在急性和嚴重的肝臟疾病中提供致病線索,潛在診斷和預后的標志物。

原文摘要:

MicroRNA Expression Profiles Related to Early Stage Murine Concanavalin A-Induced Hepatitis

Jia H.-Y· Chen F · Chen J.-Z. Wu S.-S. Wang J. Cao Q.-Y.Chen Z.Zhu H.-H

Background: Fulminant hepatitis is a severe liver disease characterized by massive hepatocyte necrosis and clinical signs of liver failure. This study explores the expression profile of microRNAs, which are regulators of a number of pathophysiological processes, during the early stage of concanavalin A (Con A)-induced hepatitis.

Methods: Balb/c mice were given ConA injections to induce fulminant hepatitis. miRNA expression profiling in liver tissues was carried out by microarray analysis. The differentially expressed miRNAs were subjected to time sequence profile analysis, gene-miRNA regulatory network analysis, and gene ontology-miRNA regulatory network analysis.

Results:Eleven miRNAs among multiClass were found to be significantly differentially expressed between liver tissue in early stage fulminant hepatitis and normal control liver tissue. Mmu-miR-133a was the most differentially expressed with the strongest regulatory ability, regulating 47 mRNAs. Mmu-miR-10a was the most highly expressed in the microRNA-GO-Network and also exerted a strong regulatory ability. The expression profiles of miR-133a and miR-10a were verified by RT-PCR.

Conclusions: These results show that, in the early stage, ConA-induced fulminant hepatitis induces a distinct miRNA expression profile. This differential miRNA expression profile may provide pathogenic clues and potential diagnostic and prognostic markers in acute and severe liver disease.

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