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Published on: September 27, 2021
Inhibition of Adhesion Molecule Gene Expression and Cell Adhesion by the Metabolic Regulator PGC-1α
Neri Minsky1, Robert G Roeder1
1Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, New York, United States of America.
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.
Insights
Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) inhibits cell adhesion molecule expression. This study reveals PGC-1α as a key molecular link between metabolic regulation and cell adhesion processes.
Area of Science:
- Molecular Biology
- Cell Biology
- Metabolic Regulation
Background:
- Cell adhesion is crucial for cell shape and function in physiological and pathological states.
- The interplay between cellular metabolism and cell adhesion is not fully understood.
- PGC-1α is a key regulator of metabolic gene expression.
Purpose of the Study:
- To investigate the role of PGC-1α in regulating cell adhesion.
- To elucidate the molecular mechanisms linking metabolism and cell adhesion.
- To identify PGC-1α as a potential mediator between these cellular networks.
Main Methods:
- Utilized cell lines, primary cells, and mouse models.
- Assessed gene expression of cell adhesion molecules.
- Performed mRNA stability and intronic RNA expression analyses.
- Investigated the role of PGC-1α's L2/L3 motifs.
- Examined the effect of PGC-1α on cell adhesion to extracellular matrix proteins.
Main Results:
- PGC-1α significantly down-regulates the expression of various cell adhesion molecules.
- Evidence suggests PGC-1α acts transcriptionally to inhibit cell adhesion genes.
- Specific PGC-1α motifs (L2/L3) are partially required for this inhibitory effect.
- PGC-1α modulates the adhesion of primary fibroblasts and hepatic stellate cells.
Conclusions:
- PGC-1α acts as an inhibitor of cell adhesion gene expression.
- A novel cross-talk exists between metabolic regulation and cell adhesion pathways.
- PGC-1α serves as a molecular link connecting cellular metabolism and cell adhesion.
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