Minsky Neri, Roeder Robert G
Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, New York, United States of America.
PLoS One. 2016 Dec 16;11(12):e0165598. doi: 10.1371/journal.pone.0165598. eCollection 2016.
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.
细胞黏附在多种生理和病理生理条件下决定细胞形状和功能方面发挥着重要作用。虽然之前有人提出代谢与细胞黏附之间存在联系，但这种相互作用的确切背景和分子细节仍未完全了解。在此我们表明，代谢基因表达的关键转录共激活因子PGC-1α可抑制细胞黏附基因的表达。利用细胞系、原代细胞和小鼠，我们发现内源性和外源性PGC-1α均可下调多种细胞黏附分子的表达。此外，通过mRNA稳定性测量以及内含子RNA表达获得的结果与PGC-1α对细胞黏附基因表达的转录作用一致。有趣的是，PGC-1α激活核激素受体所必需的L2/L3基序，对于PGC-1α抑制几种细胞黏附基因来说只是部分必需。最后，PGC-1α能够调节原代成纤维细胞和肝星状细胞与细胞外基质蛋白的黏附。我们的结果描绘了控制代谢调节的核心途径与细胞黏附之间的相互作用，并确定PGC-1α是这两个主要细胞网络之间的分子联系。
