FAK deletion accelerates liver regeneration after two-thirds partial hepatectomy

Understanding the molecular mechanisms of liver regeneration is essential to improve the survival rate of patients after surgical resection of large amounts of liver tissue. Focal adhesion kinase (FAK) regulates different cellular functions, including cell survival, proliferation and cell migration....

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Bibliographic Details
Published in:Scientific reports 2016-09, Vol.6 (1), p.34316-34316, Article 34316
Main Authors: Shang, Na, Arteaga, Maribel, Chitsike, Lennox, Wang, Fang, Viswakarma, Navin, Breslin, Peter, Qiu, Wei
Format: Article
Language:English
Subjects:
13/1
13/2
13/21
631/337
631/443
Apoptosis
Bile
Cell adhesion & migration
Cell migration
Cell survival
Clonal deletion
Epidermal growth factor receptors
Focal adhesion kinase
Hepatectomy
Humanities and Social Sciences
Liver
Liver transplantation
Molecular modelling
multidisciplinary
Science
Science (multidisciplinary)
Survival
Transplantation
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Summary:Understanding the molecular mechanisms of liver regeneration is essential to improve the survival rate of patients after surgical resection of large amounts of liver tissue. Focal adhesion kinase (FAK) regulates different cellular functions, including cell survival, proliferation and cell migration. The role of FAK in liver regeneration remains unknown. In this study, we found that Fak is activated and induced during liver regeneration after two-thirds partial hepatectomy (PHx). We used mice with liver-specific deletion of Fak and investigated the role of Fak in liver regeneration in 2/3 PHx model (removal of 2/3 of the liver). We found that specific deletion of Fak accelerates liver regeneration. Fak deletion enhances hepatocyte proliferation prior to day 3 post-PHx but attenuates hepatocyte proliferation 3 days after PHx. Moreover, we demonstrated that the deletion of Fak in liver transiently increases EGFR activation by regulating the TNFα/HB-EGF axis during liver regeneration. Furthermore, we found more apoptosis in Fak -deficient mouse livers compared to WT mouse livers after PHx. Conclusion: Our data suggest that Fak is involved in the process of liver regeneration, and inhibition of FAK may be a promising strategy to accelerate liver regeneration in recipients after liver transplantation.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep34316