Inhibition of Adhesion Molecule Gene Expression and Cell Adhesion by the Metabolic Regulator PGC-1?.

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-1?, 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-1? 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-1? on cell adhesion gene expression. Interestingly, the L2/L3 motifs of PGC-1?, necessary for nuclear hormone receptor activation, are only partly required for inhibition of several cell adhesion genes by PGC-1?. Finally, PGC-1? 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-1? as a molecular link between these two major cellular networks.

SUBMITTER: Minsky N 

PROVIDER: S-EPMC5161318 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature