MiR-122 modification enhances the therapeutic efficacy of adipose tissue-derived mesenchymal stem cells against liver fibrosis.
MiR-122 modification enhances the therapeutic efficacy of adipose tissue-derived mesenchymal stem cells against liver fibrosis.
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MiR-122修饰增强脂肪组织间充质干细胞抗肝纤维化的治疗功效
DOI：
10.1111/jcmm.13208
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发表时间：
2017-11
影响因子：
5.3
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Lou G;Yang Y;Liu F;Ye B;Chen Z;Zheng M;Liu Y
由于肝组织病理学改变复杂，单纯间充质干细胞（MSC）移植可能不足以治疗肝纤维化。鉴于miR-122通过负调节肝星状细胞（HSC）的增殖和反式激活在肝纤维化中起着至关重要的作用，本研究调查了miR-122修饰是否可以提高脂肪组织来源的MSC治疗肝纤维化的疗效。通过慢病毒介导的前体miR-122转移构建miR-122修饰的AMSC（AMSC-122）。miR-122修饰的AMSC表达高水平的miR-122，同时它们保留了其作为幼稚AMSC的表型和分化潜力。AMSC-122比scramble miRNA修饰的AMSC更有效地抑制HSC的增殖和胶原成熟。此外，AMSC衍生的外泌体介导AMSC和HSC之间的miR-122通讯，进一步影响miR-122靶基因的表达水平，如胰岛素样生长因子受体1（IGF 1 R）、细胞周期蛋白G（1）（CCNG 1）和脯氨酰-4-羟化酶α1（P4 HA 1），这些基因参与HSC的增殖和胶原成熟。此外，miR-122修饰通过抑制HSC的活化和减轻胶原沉积来增强AMSC在治疗四氯化碳（CCl 4）诱导的肝纤维化中的治疗功效。结果表明，miR-122修饰通过外泌体介导的miR-122通讯提高AMSC的治疗效果;因此，miR-122修饰是治疗肝纤维化的新的潜在策略。
Mesenchymal stem cell (MSC) transplantation alone may be insufficient for treatment of liver fibrosis because of complicated histopathological changes in the liver. Given that miR‐122 plays an essential role in liver fibrosis by negatively regulating the proliferation and transactivation of hepatic stellate cells (HSCs), this study investigated whether miR‐122 modification can improve the therapeutic efficacy of adipose tissue‐derived MSCs in treating liver fibrosis. MiR‐122‐modified AMSCs (AMSC‐122) were constructed through lentivirus‐mediated transfer of pre‐miR‐122. MiR‐122‐modified AMSCs expressed high level of miR‐122, while they retained their phenotype and differentiation potential as naïve AMSCs. AMSC‐122 more effectively suppressed the proliferation of and collagen maturation in HSCs than scramble miRNA‐modified AMSCs. In addition, AMSC‐derived exosomes mediated the miR‐122 communication between AMSCs and HSCs, further affecting the expression levels of miR‐122 target genes, such as insulin‐like growth factor receptor 1 (IGF1R), Cyclin G(1) (CCNG1) and prolyl‐4‐hydroxylase α1 (P4HA1), which are involved in proliferation of and collagen maturation in HSCs. Moreover, miR‐122 modification enhanced the therapeutic efficacy of AMSCs in the treatment of carbon tetrachloride (CCl4)‐induced liver fibrosis by suppressing the activation of HSCs and alleviating collagen deposition. Results demonstrate that miR‐122 modification improves the therapeutic efficacy of AMSCs through exosome‐mediated miR‐122 communication; thus, miR‐122 modification is a new potential strategy for treatment of liver fibrosis.
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影响因子：
25.7
作者：
Bala S;Csak T;Saha B;Zatsiorsky J;Kodys K;Catalano D;Satishchandran A;Szabo G
通讯作者：
Szabo G
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作者：
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