Axis of serotonin -pERK-YAP in liver regeneration

Regeneration Defects in Yap and Taz Mutant Mouse Livers Are Caused by Bile Duct Disruption and Cholestasis

“…The minimal requirement for YAP/TAZ in hepatocytes during liver regeneration after toxic injury creates a conundrum because YAP/TAZ are transiently activated in hepatocytes in response to liver injury. 2,[7][8][9][10][11][12][13] Although YAP/ TAZ can act redundantly with other signaling pathways that are activated during liver regeneration, 46 YAP/TAZ can also regulate processes that are not easily assayed. For example, YAP/TAZ activation can increase the competitive fitness of noninjured hepatocytes, thereby selecting the fitter cells for proliferation 5,47 or YAP/TAZ can prime hepatocytes for transdifferentiation into liver progenitor cells or BECs.…”

“…In contrast to embryonic development, it appears that YAP/TAZ are essential for regeneration in different organs, where they can play an instructive role in driving regenerative cell proliferation. 1 In the liver, YAP is transiently activated in hepatocytes upon different types of liver injury, 2,[7][8][9][10][11][12][13] and experimental hyperactivation of YAP/TAZ in hepatocytes improved liver regrowth after partial hepatectomy. 14,15 Conversely, liver-specific deletion of Yap (and Taz) reduced and/or delayed regenerative cell proliferation of hepatocytes after different types of liver damage, such as that caused by partial hepatectomy, toxic liver injury, and bile duct ligation (BDL).…”

Context-dependent roles of YAP/TAZ in stem cell fates and cancer

“…For example, colonic regeneration in a mouse model of colitis and restoration of the adult heart post-myocardial infarction involves YAP and Lgr5 + stem cells in intestinal tissues, and organoids undergo expansion after injury in a YAP-dependent manner [71][72][73][74][75]. Also, YAP is critical for regeneration in the lung after damage to the alveolar epithelium, in the liver for hepatocytes to reprogram into biliary progenitors after the injury, and in the retina for Müller glia to proliferate after eye injury [76][77][78][79][80][81]. In several of the aforementioned examples, the mechanism by which YAP promotes regeneration is not elucidated.…”

5-HT and Intraplatelet 5-HT: a potential upstream regulator of YAP in liver regeneration

“…Additionally, YAP expression was lower in TPH1 −/− mice then in WT mice, especially in the first three days after PH. Finally, we showed that the 5-HT-pERK-YAP axis might be involved in liver regeneration 6 . Thus, we hypothesized that 5-HT might be an upregulator of YAP in liver regeneration.…”