Mesenchymal stromal cells may promote lipid utilization via increment of mitochondria biogenesis in targeted hepatocytes
Mesenchymal stromal cells may promote lipid utilization via increment of mitochondria biogenesis in targeted hepatocytes
复制标题
间充质基质细胞可能通过增加目标肝细胞中的线粒体生物发生来促进脂质利用
DOI：
10.1055/s-0039-3402133
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Christ B
中科院分区：
文献类型：
--
作者：
Hsu MJ;Christ M;Christ B
方法：原代小鼠肝细胞和人骨髓间充质干细胞在脂肪变性诱导的蛋氨酸胆碱缺乏（MCD）培养基中单独和共培养。结果：与MSC单独培养相比，MSC与肝细胞共培养对TNT的诱导因子TNFα诱导蛋白2（TNFAIP 2）和RAS样原癌基因A（RALA）的表达无明显影响。在MSC中，PPARγ共激活因子1α（PPARGC 1A; PGC 1 α）和其他线粒体生物发生标志物如线粒体转录因子A（TFAM）和血红素加氧酶-1（HMOX 1）均未发生改变。然而，在小鼠肝细胞中，PGC 1 α（线粒体生物合成的调节因子）的表达在共培养中比单独的肝细胞增强。结论：人MSC可能通过TNT将线粒体从MSC转移到肝细胞而增加小鼠肝细胞中脂质的降解。运输可以通过微管为基础的，但不是肌动蛋白为基础的货物运输。递送的人线粒体可诱导小鼠肝细胞中线粒体的生物发生，并因此提高参与脂肪酸氧化的基因的表达以引起脂质利用。因此，本文的结果可能支持MSC衍生的线粒体移植促进脂肪肝中脂质分解的潜力。
Methods:Mono-and co-cultures of primary mouse hepatocytes and human bone marrow-derived MSC were grown in steatosis-inducing methionine-choline-deficient (MCD) medium. To understand the involvement of actin, a major component of TNT, expression of genes involved in actin-dependent TNT transportation and of markers involved in mitochondria biogenesis was examined by RT-PCR using human-and mouse-specific primer pairs.Results:Compared with MSC alone, the co-culture of hepatocytes and MSC did not impact on inducers of actin-based TNT, namely TNFα-induced protein 2 (TNFAIP2) and RAS like proto-oncogene A (RALA), in the MSC. Neither PPARγ coactivator 1α (PPARGC1A; PGC1α) nor other markers of mitochondrial biogenesis such as mitochondrial transcription factor A (TFAM) and heme oxygenase-1 (HMOX1) were altered in the MSC. Yet, in the mouse hepatocytes, the expression of PGC1α, a regulator of mitochondria biogenesis, was enhanced in co-culture as compared with hepatocytes alone.Conclusion:Human MSC may increase the degradation of lipids in mouse hepatocytes by mitochondria transfer from the MSC to the hepatocytes via TNT. Transport may be achieved by microtubule-based, but not actin-based cargo transport. The delivered human mitochondria may induce the biogenesis of mitochondria in the mouse hepatocytes, and thus elevate the expression of genes involved in fatty acid oxidation to elicit lipid utilization. Thus, the results presented here may support the potential of MSC-derived mitochondria transplantation to foster lipid breakdown in fatty livers.