Effects of Exosomes Derived from Adipose-Derived Mesenchymal Stem Cells on Pyroptosis and Regeneration of Injured Liver.
Effects of Exosomes Derived from Adipose-Derived Mesenchymal Stem Cells on Pyroptosis and Regeneration of Injured Liver.
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脂肪间充质干细胞来源的Exosomes对肝损伤后肝细胞凋亡和再生的影响。
DOI：
10.3390/ijms232012065
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发表时间：
2022-10-11
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
虽然越来越多的证据表明外泌体对肝脏缺血再灌注损伤（HIRI）具有积极的治疗作用，但基于抑制细胞凋亡的脂肪间充质干细胞（ADSCs-Exo）来源的外泌体减轻肝脏损伤的研究尚未报道。外泌体含有不同种类的生物活性物质，如蛋白质、脂质、mRNA、miRNA和信号分子。这些分子广泛参与细胞间通讯、细胞信号传递、增殖、迁移和凋亡。因此，我们研究了ADSCs-Exo在大鼠肝脏部分切除损伤的缺血再灌注后所产生的积极作用。本研究发现，术后尾静脉注射ADSCs-Exo可有效抑制NLRP 3、ASC、caspase-1、GSDMD-N等脓毒症相关因子的表达，促进Cyclin D1、VEGF等再生相关因子的表达。此外，我们发现上述细胞活性与NF-κB和Wnt/β-catenin信号通路有关。结果表明，ADSCs和ADSCs-Exo能减少损伤肝脏的焦亡，促进肝再生相关因子的表达，抑制NF-κB通路，激活Wnt/β-catenin通路。然而，尽管脂肪间充质干细胞（ADSC）移植可以减轻肝损伤，但它导致了热解相关蛋白GSDMD-N表达的显着增加。综上所述，本研究表明ADSCs-Exo作为替代干细胞的无细胞疗法具有独特的优势和意义，在肝损伤的临床诊断和治疗中仍具有广阔的研究前景。
Although accumulating evidence indicates that exosomes have a positive therapeutic effect on hepatic ischemia–reperfusion injury (HIRI), studies focusing on the alleviation of liver injury by exosomes derived from adipose-derived mesenchymal stem cells (ADSCs-Exo) based on the inhibition of cell pyroptosis have not yet been reported. Exosomes contain different kinds of biologically active substances such as proteins, lipids, mRNAs, miRNAs, and signaling molecules. These molecules are widely involved in cell–cell communication, cell signal transmission, proliferation, migration, and apoptosis. Therefore, we investigated the positive effects exerted by ADSCs-Exo after hepatic ischemia–reperfusion with partial resection injury in rats. In this study, we found that the post-operative tail vein injection of ADSCs-Exo could effectively inhibit the expression of pyroptosis-related factors such as NLRP3, ASC, caspase-1, and GSDMD-N, and promote the expression of regeneration-related factors such as Cyclin D1 and VEGF. Moreover, we found that the above cellular activities were associated with the NF-κB and Wnt/β-catenin signaling pathways. According to the results, ADSCs and ADSCs-Exo can reduce pyroptosis in the injured liver and promote the expression of those factors related to liver regeneration, while they can inhibit the NF-κB pathway and activate the Wnt/β-catenin pathway. However, although adipose-derived mesenchymal stem cell (ADSC) transplantation can reduce liver injury, it leads to a significant increase in the pyroptosis-related protein GSDMD-N expression. In conclusion, our study shows that ADSCs-Exo has unique advantages and significance as a cell-free therapy to replace stem cells and still has a broad research prospect in the clinical diagnosis and treatment of liver injuries.
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