Abstract:Nature Communications 8 Article number: 16017 (2017); Published: 6 July 2017; Updated: 7 August 2017. The financial support for this Article was not fully acknowledged. The Acknowledgements should have included the following: This work was supported by a Nanken-Kyoten grant from Tokyo Medical and Dental University (TMDU).
“…Interestingly, LSECs are also important in maintaining cell integrity after YAP activation in single hepatocytes. Combined hepatocyte and LSEC damage induced by ethanol – but not damage of hepatocytes or LSECs alone – changes the fate of YAP-activated hepatocytes from proliferation to apoptosis ( Miyamura et al, 2017 ). YAP activation in LSECs has been shown to govern protein expression of HIF-1α and VEGF-A to promote angiogenesis in fibrosis – a process blocking nutrient transport from sinusoids and exacerbating the liver injury ( Elpek, 2015 ; Zhang C. et al, 2018 ).…”
Section: Liver Fibrosis – the Scarring Face Of Yap And Tazmentioning
The first description of Hippo signaling in mammals a little more than 10 years ago showed a striking phenotype in the liver, linking the role of this signaling pathway to organ size control and carcinogenesis. Even though Hippo signaling has been extensively studied in the liver and other organs over the recent years, many open questions remain in our understanding of its role in hepatic physiology and disease. The functions of Hippo signaling extend well beyond cancer and organ size determination: components of upstream Hippo signaling and the downstream effectors YAP and TAZ are involved in a multitude of cell and non-cell autonomous functions including cell proliferation, survival, development, differentiation, metabolism, and cross-talk with the immune system. Moreover, regulation and biological functions of Hippo signaling are often organ or even cell type specific – making its role even more complex. Here, we give a concise overview of the role of Hippo signaling in the liver with a focus on cell-type specific functions. We outline open questions and future research directions that will help to improve our understanding of this important pathway in liver disease.
“…Interestingly, LSECs are also important in maintaining cell integrity after YAP activation in single hepatocytes. Combined hepatocyte and LSEC damage induced by ethanol – but not damage of hepatocytes or LSECs alone – changes the fate of YAP-activated hepatocytes from proliferation to apoptosis ( Miyamura et al, 2017 ). YAP activation in LSECs has been shown to govern protein expression of HIF-1α and VEGF-A to promote angiogenesis in fibrosis – a process blocking nutrient transport from sinusoids and exacerbating the liver injury ( Elpek, 2015 ; Zhang C. et al, 2018 ).…”
Section: Liver Fibrosis – the Scarring Face Of Yap And Tazmentioning
The first description of Hippo signaling in mammals a little more than 10 years ago showed a striking phenotype in the liver, linking the role of this signaling pathway to organ size control and carcinogenesis. Even though Hippo signaling has been extensively studied in the liver and other organs over the recent years, many open questions remain in our understanding of its role in hepatic physiology and disease. The functions of Hippo signaling extend well beyond cancer and organ size determination: components of upstream Hippo signaling and the downstream effectors YAP and TAZ are involved in a multitude of cell and non-cell autonomous functions including cell proliferation, survival, development, differentiation, metabolism, and cross-talk with the immune system. Moreover, regulation and biological functions of Hippo signaling are often organ or even cell type specific – making its role even more complex. Here, we give a concise overview of the role of Hippo signaling in the liver with a focus on cell-type specific functions. We outline open questions and future research directions that will help to improve our understanding of this important pathway in liver disease.
“…Although promoting hepatocyte proliferation is generally beneficial for repopulating tissues, the precise consequences of YAP/TAZ activity depend on the overall health of the liver microenvironment. For example, sustained or excessive YAP overexpression in an injured liver may paradoxically lead to the elimination of proliferating hepatocytes as part of the injury response (Miyamura et al 2017 ). Fig.…”
Section: Cell-type Specific Roles Of Yap/taz In Liver Diseasementioning
Metabolic dysfunction-associated steatotic liver disease (MASLD) is becoming an increasingly pressing global health challenge, with increasing mortality rates showing an upward trend. Two million deaths occur annually from cirrhosis and liver cancer together each year. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), key effectors of the Hippo signaling pathway, critically regulate tissue homeostasis and disease progression in the liver. While initial studies have shown that YAP expression is normally restricted to cholangiocytes in healthy livers, the activation of YAP/TAZ is observed in other hepatic cells during chronic liver disease. The disease-driven dysregulation of YAP/TAZ appears to be a critical element in the MASLD progression, contributing to hepatocyte dysfunction, inflammation, and fibrosis. In this study, we focused on the complex roles of YAP/TAZ in MASLD and explored how the YAP/TAZ dysregulation of YAP/TAZ drives steatosis, inflammation, fibrosis, and cirrhosis. Finally, the cell-type-specific functions of YAP/TAZ in different types of hepatic cells, such as hepatocytes, hepatic stellate cells, hepatic macrophages, and biliary epithelial cells are discussed, highlighting the multifaceted impact of YAP/TAZ on liver physiology and pathology.
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