title: Actin organization and hepatocyte differentiation are regulated by extracellular matrix via PI-4,5-bisphosphate in the rat.
abstract: 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]P2) 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)P2 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)P2 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)P2 is involved in the regulation of hepatocyte differentiation by the ECM.
authors.affiliation: First Department of Internal Medicine, Gifu University School of Medicine, Gifu 501-1194, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kimata
authors.forename: Masahito
authors.initials: M
authors.lastname: Nagaki
authors.forename: Tomio
authors.initials: T
authors.lastname: Ogiso
authors.forename: Takafumi
authors.initials: T
authors.lastname: Naiki
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kato
authors.forename: Hisataka
authors.initials: H
authors.lastname: Moriwaki
mesh_terms: D000199:Actins / Q000378:metabolism*; D000418:Albumins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D002454:Cell Differentiation; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism*; D015870:Gene Expression; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D000199:Actins; D000418:Albumins; D051557:Hepatocyte Nuclear Factor 4; D019269:Phosphatidylinositol 4,5-Diphosphate; D012313:RNA