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Actin organization and hepatocyte differentiation are regulated by extracellular matrix via PI‐4,5‐bisphosphate in the rat
Author(s) -
Kimata Takayuki,
Nagaki Masahito,
Ogiso Tomio,
Naiki Takafumi,
Kato Tomohiro,
Moriwaki Hisataka
Publication year - 2006
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.21215
Subject(s) - gelsolin , microbiology and biotechnology , extracellular matrix , hepatocyte , biology , actin cytoskeleton , cytoskeleton , actin , cell , biochemistry , in vitro
Cell adhesion to the extracellular matrix (ECM) plays vital roles in both morphogenesis and regulation of gene expression in cells of adult organisms. How intracellular, cytoskeletal, and signaling factors connect and communicate with the ECM is a fundamental question. Using a cDNA microarray analysis, we identified phosphatidylinositol 4,5‐bisphosphate (PI[4,5]P 2 ) phosphatase mRNA as being up‐regulated in hepatocytes cultured on a basement membrane matrix, Engelbreth‐Holm‐Swarm (EHS) gel, which led to the finding that the PI(4,5)P 2 levels of hepatocytes decreased on EHS gel. These changes in hepatocytes on EHS gel were accompanied by promotion of actin depolymerization and differentiated phenotypes of the hepatocytes. Treatment with PI(4,5)P 2 or a phospholipase C inhibitor, U73122, resulted in decreased mRNA expressions of albumin and hepatocyte nuclear factor 4 (HNF‐4) in hepatocytes. In contrast, actin‐disrupting agent gelsolin increased mRNA expressions of albumin and HNF‐4. In conclusion , organization of the actin cytoskeleton via PI(4,5)P 2 is involved in the regulation of hepatocyte differentiation by the ECM. (H EPATOLOGY 2006;44:140–151.)