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Enhanced liver regeneration following changes induced by hepatocyte‐specific genetic ablation of integrin‐linked kinase
Author(s) -
Apte Udayan,
Gkretsi Vasiliki,
Bowen William C.,
Mars Wendy M.,
Luo JianHua,
Donthamsetty Shashikiran,
Orr Ann,
Monga Satdarshan P.S.,
Wu Chuanyue,
Michalopoulos George K.
Publication year - 2009
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.23059
Subject(s) - liver regeneration , integrin linked kinase , regeneration (biology) , hepatocyte , microbiology and biotechnology , hepatectomy , biology , signal transduction , kinase , chemistry , cancer research , endocrinology , medicine , protein kinase a , biochemistry , cyclin dependent kinase 2 , surgery , resection , in vitro
Following liver regeneration after partial hepatectomy, liver grows back precisely to its original mass and does not exceed it. The mechanism regulating this “hepatostat” is not clear and no exceptions have been found to date. Although pathways initiating liver regeneration have been well studied, mechanisms involved in the termination of liver regeneration are unclear. Here, we report that integrin‐linked kinase (ILK) (involved in transmission of the extracellular matrix [ECM] signaling by way of integrin receptors) and/or hepatic adaptations that ensue following ILK hepatocyte‐targeted removal are critical for proper termination of liver regeneration. Following partial hepatectomy (PHx), mice with a liver‐specific ILK ablation (ILK‐KO‐Liver) demonstrate a termination defect resulting in 58% larger liver than their original pre‐PHx mass. This increase in post‐PHx liver mass is due to sustained cell proliferation driven in part by increased signaling through hepatocyte growth factor (HGF), and the β‐catenin pathway and Hippo kinase pathways. Conclusion: The data indicate that ECM‐mediated signaling by way of ILK is essential in proper termination of liver regeneration. This is the first evidence of a defect leading to impaired termination of regeneration and excessive accumulation of liver weight following partial hepatectomy. (H EPATOLOGY 2009.)