TY - JOUR
T1 - Axis of serotonin -pERK-YAP in liver regeneration
AU - Fang, Yu
AU - Liu, Chun
AU - Shu, Bo
AU - Zhai, Mimi
AU - Deng, Chaolin
AU - He, Chao
AU - Luo, Ming
AU - Han, Tong
AU - Zheng, Wei
AU - Zhang, Jingyao
AU - Liu, Sushun
N1 - Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/9/15
Y1 - 2018/9/15
N2 - 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.
AB - 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.
KW - Liver regeneration
KW - Phospho-extracellular signal-regulated kinases
KW - Serotonin
KW - TPH1 mice
KW - Yes-associated protein
UR - https://www.scopus.com/pages/publications/85052154551
U2 - 10.1016/j.lfs.2018.08.047
DO - 10.1016/j.lfs.2018.08.047
M3 - 文章
C2 - 30142376
AN - SCOPUS:85052154551
SN - 0024-3205
VL - 209
SP - 490
EP - 497
JO - Life Sciences
JF - Life Sciences
ER -