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Role of IPP (Integrin linked kinase‐Parvin‐Pinch) complex in regulating hepatocyte survival and liver size
Author(s) -
Donthamsetty Shashi,
Mars Wendy M.,
Wu Cary,
Michalopoulos George K.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.115.5
Subject(s) - integrin linked kinase , hepatocyte , apoptosis , kinase , liver regeneration , hepatocyte growth factor , biology , in vivo , medicine , chemistry , endocrinology , microbiology and biotechnology , cancer research , protein kinase a , receptor , regeneration (biology) , in vitro , biochemistry , cyclin dependent kinase 2
This study investigates the role of IPP (Integrin linked kinase‐Parvin‐Pinch) complex in hepatocyte survival and regulation of final liver size. We found that hepatocyte specific ILK KO mice (Integrin linked kinase) died much later than WT mice after challenge with a lethal dose of Fas agonist Jo‐2. At sublethal dose of Jo‐2, all KO mice survived with minimal apoptosis whereas WT mice developed extensive apoptosis with 30% mortality at 12 h. Proteins known to be associated with cell survival/death were differentially expressed in the 2 groups. Next, we investigated the role of IPP complex in regulating the liver size. We generated liver specific Pinch1/2 KO mice. After ablation of Pinch1/2, animals are born normal. Soon after birth, however, they develop histologic abnormalities characterized by disorderly hepatic plates, increased proliferation of hepatocytes and biliary cells, and increased deposition of extracellular matrix. By the end of 17 weeks the pinch1/2 KO mice end with a liver to body weight ratio twice as much as the WT mice. These results are similar to those of mice with deletion of another member of the IPP complex, ILK. Our results show in vivo the significance of IPP complex for regulation of hepatocyte survival and liver size. The work is supported by a R01 grant (5R01CA035373‐26) titled “HGF in Liver Development, Regeneration and Neoplasia”