Yu Fang1, Chun Liu2, Bo Shu2, Mimi Zhai3, Chaolin Deng2, Chao He2, Ming Luo2, Tong Han2, Wei Zheng3, Jingyao Zhang3, Sushun Liu4. 1. 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. 2. Department of General Surgery, the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China. 3. Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. 4. Department of General Surgery, the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China; Department of Hepatobiliary Surgery, Shaanxi Province Hospital, Xi'an, Shaanxi 710068, China. Electronic address: surun9566@csu.edu.cn.
Abstract
BACKGROUND AND AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND AND AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.