title: Inhibition of Adhesion Molecule Gene Expression and Cell Adhesion by the Metabolic Regulator PGC-1α.
abstract: Cell adhesion plays an important role in determining cell shape and function in a variety of physiological and pathophysiological conditions. While links between metabolism and cell adhesion were previously suggested, the exact context and molecular details of such a cross-talk remain incompletely understood. Here we show that PGC-1α, a pivotal transcriptional co-activator of metabolic gene expression, acts to inhibit expression of cell adhesion genes. Using cell lines, primary cells and mice, we show that both endogenous and exogenous PGC-1α down-regulate expression of a variety of cell adhesion molecules. Furthermore, results obtained using mRNA stability measurements as well as intronic RNA expression are consistent with a transcriptional effect of PGC-1α on cell adhesion gene expression. Interestingly, the L2/L3 motifs of PGC-1α, necessary for nuclear hormone receptor activation, are only partly required for inhibition of several cell adhesion genes by PGC-1α. Finally, PGC-1α is able to modulate adhesion of primary fibroblasts and hepatic stellate cells to extracellular matrix proteins. Our results delineate a cross talk between a central pathway controlling metabolic regulation and cell adhesion, and identify PGC-1α as a molecular link between these two major cellular networks.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, New York, United States of America.
authors.forename: Neri
authors.initials: N
authors.lastname: Minsky
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, New York, United States of America.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Roeder
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002460:Cell Line; D015870:Gene Expression; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000737:chemistry
chemical_list: D015815:Cell Adhesion Molecules; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D012333:RNA, Messenger