title: Integrin-linked kinase is involved in matrix-induced hepatocyte differentiation.
abstract: Hepatocytes have restricted proliferative capacity in culture and when cultured without matrix, lose the hepatocyte-specific gene expression and characteristic cellular micro-architecture. Overlay of matrix-preparations on de-differentiated hepatocytes restores differentiation. Integrin-linked kinase (ILK) is a cell-matrix-adhesion protein crucial in fundamental processes such as differentiation and survival. In this study, we investigated the role of ILK, and its binding partners PINCH, alpha-parvin, and Mig-2 in matrix-induced hepatocyte differentiation. We report here that ILK is present in the liver and localizes at cell-matrix adhesions of cultured hepatocytes. We also show that ILK, PINCH, alpha-parvin, and Mig-2 expression level is dramatically reduced in the re-differentiated hepatocytes. Interestingly, hepatocytes lacking ILK undergo matrix-induced differentiation but their differentiation is incomplete, as judged by monitoring cell morphology and production of albumin. Our results show that ILK and cell-matrix adhesion proteins play an important role in the process of matrix-induced hepatocyte differentiation.
authors.affiliation: Department of Cellular and Molecular Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Gkretsi
authors.forename: William C
authors.initials: WC
authors.lastname: Bowen
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
authors.forename: Chuanyue
authors.initials: C
authors.lastname: Wu
authors.forename: George K
authors.initials: GK
authors.lastname: Michalopoulos
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology; D004338:Drug Combinations; D005109:Extracellular Matrix / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D007797:Laminin / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000096:biosynthesis; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011509:Proteoglycans / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D000099200:Scaffold Protein ILK
chemical_list: D002352:Carrier Proteins; D003094:Collagen; D004338:Drug Combinations; D007797:Laminin; D008840:Microfilament Proteins; D017346:Protein Serine-Threonine Kinases; D011509:Proteoglycans; D000099200:Scaffold Protein ILK; C517887:Parva protein, rat; C059485:matrigel