Department of General Surgery, the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Department of General Surgery, Anhui Provincial Hospital, Hefei, Anhui 230031, China.
Department of General Surgery, the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
Life Sci. 2018 Sep 15;209:490-497. doi: 10.1016/j.lfs.2018.08.047. Epub 2018 Aug 21.
Serotonin and YAP exhibit a vital role in regulating cell proliferation and wound-healing response. The aim of the study was to investigate whether 5-HT could promote liver regeneration by activating YAP.
PH models were established by WT and TPH1-/- mice. ELISA, RT-PCR, western blot, immunohistochemistry, flow cytometry and MTT assay were used to assess the level of 5-HT and YAP and proliferation after PH.
We found that 5-HT level was lower in the serum and liver of TPH1-/- mice. After PH, TPH1-/- mice, lacking in 5-HT, demonstrated worse regenerative ability and suffered more severe liver injury. Additionally, YAP expression was also lower in TPH1-/- mice. Moreover, we found that YAP expression was prominent within the first three days following PH. Similarly, 5-HT could promote cell proliferation by upregulating YAP expression in L-O2 cells. As predicted, using YAP-siRNA sharply reduced the proliferative capacity mediated by 5-HT. Further study also indicated that ERK participated in the regulation of YAP induced by 5-HT. By using an ERK inhibitor, the YAP expression and cell proliferation induced by 5-HT were both suppressed. Although YAP-siRNA was used to block YAP expression, pERK and ERK expression were not affected. Taken together, these data showed that 5-HT contributed to liver regeneration by regulating YAP expression, which at least in part, was by activation of pERK.
A role of the 5-HT-pERK-YAP axis in liver regeneration emerged from our study and might be a potential target to promote regeneration and injury repair.
血清素（5-HT）和 Yes 相关蛋白（YAP）在调节细胞增殖和伤口愈合反应方面发挥着重要作用。本研究旨在探讨 5-HT 是否可以通过激活 YAP 促进肝脏再生。
使用 WT 和 TPH1-/- 小鼠建立 PH 模型。采用 ELISA、RT-PCR、western blot、免疫组化、流式细胞术和 MTT 检测法评估 PH 后血清和肝脏中 5-HT 和 YAP 水平及增殖情况。
我们发现 TPH1-/- 小鼠血清和肝脏中的 5-HT 水平较低。PH 后，缺乏 5-HT 的 TPH1-/- 小鼠表现出更差的再生能力和更严重的肝损伤。此外，TPH1-/- 小鼠中 YAP 的表达也较低。此外，我们发现 YAP 的表达在 PH 后前三天较为明显。同样，5-HT 可以通过上调 L-O2 细胞中 YAP 的表达来促进细胞增殖。正如预测的那样，使用 YAP-siRNA 可显著降低 5-HT 介导的增殖能力。进一步的研究还表明，ERK 参与了 5-HT 诱导的 YAP 调节。使用 ERK 抑制剂可抑制 5-HT 诱导的 YAP 表达和细胞增殖。虽然使用 YAP-siRNA 阻断了 YAP 的表达，但 pERK 和 ERK 的表达并未受到影响。总之，这些数据表明，5-HT 通过调节 YAP 表达促进肝脏再生，这至少部分是通过激活 pERK 实现的。
本研究发现 5-HT-pERK-YAP 轴在肝脏再生中起作用，可能成为促进再生和损伤修复的潜在靶点。
