Circulating extracellular vesicles contain liver-derived RNA species as indicators of severe cholestasis-induced early liver fibrosis in mice

Posted: 2021-11-15 20:00:00
Aims Biliary diseases represent around 10% of all chronic liver diseases and affect both adults and children. Currently available biochemical tests detect cholestasis but not early liver fibrosis. Circulating extracellular vesicles (EVs) provide a non-invasive, real-time molecular snapshot of the injured organ. We thus aimed at searching for a panel of EV-based biomarkers for cholestasis-induced early liver fibrosis using mouse models. Results: Progressive and detectable histological evidence of collagen deposition and liver fibrosis was observed as from Day 8 after bile duct ligation (BDL) in mice. Whole transcriptome and small RNA-seq analyses of circulating EVs revealed differentially enriched RNA species after BDL versus sham controls. Unsupervised hierarchical clustering identified a signature that allowed for discrimination between BDL and controls. In particular, 151 microRNAs enriched in BDL-derived EVs were identified, of which 66 were conserved in humans. The liver was an important source of circulating EVs in BDL animals as evidenced by the enrichment of several hepatic mRNAs, such as Albumin and Haptoglobin. Interestingly, among experimentally validated miRNAs, miR192-5p, miR194-5p, miR22-3p and miR29a-3p showed similar enrichment patterns also in EVs derived from DDC-treated (drug-induced severe cholestasis) but not in mice with mild phenotype or non-cholestatic liver fibrosis. Innovation A panel of mRNAs and miRNAs contained in circulating EVs, when combined, indicate hepatic damage and fibrosis in mice, and represent promising biomarkers for human severe cholestasis-induced liver fibrosis. Conclusion Analysis of EV-based miRNAs, in combination with hepatic injury RNA markers, can detect early cholestatic liver injury and fibrosis in mice.

参考サイト PubMed: exsome


8月 19, 2020 バイオアソシエイツ


7月20〜22日に開催されたISEV2020仮想年次総会(International Society for Extracellular Vesicles)で、フランス・ストラスブール大学のJacky Goetz博士の腫瘍メカニクスラボに所属するShima Ghoroghi氏(写真)は、「Ral-GTPaseは、 エクソソーム の生合成と臓器向性を制御することにより転移を促進する(Ral-GTPases Promote Metastasis by Controlling Biogenesis and…

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