Human amniotic mesenchymal stromal cells alleviate acute liver injury by inhibiting the pro-inflammatory response of liver resident macrophage through autophagy
Human amniotic mesenchymal stromal cells alleviate acute liver injury by inhibiting the pro-inflammatory response of liver resident macrophage through autophagy
复制标题
人羊膜间充质基质细胞通过自噬抑制肝脏驻留巨噬细胞的促炎反应，减轻急性肝损伤
DOI：
10.21037/atm.2019.08.83
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发表时间：
2019-08-01
影响因子：
--
通讯作者：
Yu, Yue
中科院分区：
文献类型：
--
作者：
Hua, Dongxu;Ju, Zheng;Yu, Yue
背景：巨噬细胞的激活和极化在毒素引起的肝损伤的发病机制中至关重要。人羊膜间充质基质细胞（hAMSCs）是新发现的间充质干细胞，已被证明对多种自身免疫性疾病具有免疫调节能力。方法：给小鼠腹腔注射对乙酰氨基酚（APAP）建立肝损伤模型。通过尾静脉注射hAMSCs，通过肝功能和病理分析观察肝功能。为了测试hAMSCs的体外调节能力，收集hAMSCs的上清液并与Kupffer细胞（KCs）共培养。采用脂质体消除体内KCs的功能。结果：hAMSCs输注可降低APAP诱导的肝损伤中的肝功能损伤水平和炎症表达。 hAMSCs 在体外显着促进 KCs 的 M2 极化而不是 M1 极化。此外，机制研究还证明 hAMSC 减少自噬，如下调 LC3B-II 水平所揭示的。体内KCs的消除消除了hAMSCs对肝损伤的保护能力，导致肝脏发病机制显着增加，丙氨酸氨基转氨酶（ALT）和天冬氨酸氨基转氨酶（AST）水平升高。结论：我们的结果证明，在APAP处理的肝脏模型中，hAMSCs通过调节自噬抑制KCs的M1极化并促进KCs的M2极化。这样，肝脏的损伤就减轻了。该研究为急性肝损伤疾病的治疗提供了新的策略。
Background: The activation and polarization of macrophages are crucial during the pathogenesis of liver injury induced by the toxin. Human amniotic mesenchymal stromal cells (hAMSCs) are newly identified mesenchymal stem cells and have been shown to have an immunoregulatory ability for multiple autoimmune diseases.Methods: Mice were intraperitoneally injected with Acetaminophen (APAP) to establish a liver injury model. hAMSCs were injected through the tail vein, and the liver function was observed through a liver function and pathology analysis. To test the regulative ability of hAMSCs in vitro, the supernatant of hAMSCs were collected and co-cultured with Kupffer cells (KCs). Liposome was used to abolish the function of KCs in vivo.Results: Infusion of hAMSCs reduced the level of liver function injury and inflammation expression in APAP-induced liver injury. hAMSCs markedly promoted M2 polarization of KCs instead of M1 polarization in vitro. Furthermore, the mechanism study also proved that hAMSCs reduced autophagy, as revealed by down-regulated LC3B-II levels. The elimination of KCs in vivo abolished the protective ability of hAMSCs in liver injury, which resulted in a significant increase of liver pathogenesis along with an increase in alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST) levels.Conclusions: Our results proved that hAMSCs suppressed M1 polarization and promoted M2 polarization of KCs through regulating autophagy in the model of APAP-treated livers. Thus, the injury of the liver was attenuated. This study provides us a new therapeutic strategy for the disease of acute liver injury.