The roles and interactions of platelets and liver sinusoidal endothelial cells in liver regeneration are unclear, and the trigger that initiates hepatocyte proliferation is unknown. We aimed to identify the key factors released by activated platelets that induce liver sinusoidal endothelial cells to produce interleukin-6 (IL-6), a cytokine implicated in the early phase of liver regeneration. We characterized the releasate of activated platelets inducing the in vitro production of IL-6 by mouse liver sinusoidal endothelial cells and observed that the stimulating factor was a thermolabile protein. Following gel filtration, a single fraction of activated platelet releasate induced a maximal IL-6 secretion by liver sinusoidal endothelial cells (90.2 ± 13.9 versus control with buffer, 9.0 ± 0.8 pg/mL, p < 0.05). Mass spectroscopy analysis of this fraction, followed by in silico processing, resulted in a reduced list of 18 candidates. Several proteins from the list were tested, and only recombinant transforming growth factor β1 (TGF-β1) resulted in an increased IL-6 production up to 242.7 ± 30.5 pg/mL, which was comparable to non-fractionated platelet releasate effect. Using neutralizing anti-TGF-β1 antibody or a TGF-β1 receptor inhibitor, IL-6 production by liver sinusoidal endothelial cells was dramatically reduced. These results support a role of platelet TGF-β1 β1 in the priming phase of liver regeneration.

中文翻译：

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血小板转化生长因子-β1 诱导肝窦内皮细胞分泌白细胞介素 6。

血小板和肝窦内皮细胞在肝再生中的作用和相互作用尚不清楚，启动肝细胞增殖的触发因素尚不清楚。我们的目的是确定活化血小板释放的关键因子，诱导肝窦内皮细胞产生白细胞介素 6 (IL-6)，这是一种与肝再生早期阶段有关的细胞因子。我们对诱导小鼠肝窦内皮细胞体外产生 IL-6 的活化血小板的释放进行了表征，并观察到刺激因子是一种不耐热的蛋白质。凝胶过滤后，活化的血小板释放物的单一部分诱导肝窦内皮细胞最大程度地分泌IL-6（90.2±13.9与缓冲液对照相比，9.0±0.8pg/mL，p<0.05 ）。对这部分进行质谱分析，然后进行计算机处理，得到了 18 种候选物质的精简列表。对列表中的几种蛋白质进行了测试，只有重组转化生长因子 β1 (TGF-β1) 导致 IL-6 产量增加至 242.7 ± 30.5 pg/mL，这与非分级血小板释放效果相当。使用中和性抗 TGF-β1 抗体或 TGF-β1 受体抑制剂，肝窦内皮细胞产生的 IL-6 显着减少。这些结果支持血小板 TGF-β1 β1 在肝再生启动阶段的作用。