GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:17878231

From GONUTS
Jump to: navigation, search
Citation

Chen, CL, Liu, IH, Fliesler, SJ, Han, X, Huang, SS and Huang, JS (2007) Cholesterol suppresses cellular TGF-beta responsiveness: implications in atherogenesis. J. Cell. Sci. 120:3509-21

Abstract

Hypercholesterolemia is a major causative factor for atherosclerotic cardiovascular disease. The molecular mechanisms by which cholesterol initiates and facilitates the process of atherosclerosis are not well understood. Here, we demonstrate that cholesterol treatment suppresses or attenuates TGF-beta responsiveness in all cell types studied as determined by measuring TGF-beta-induced Smad2 phosphorylation and nuclear translocation, TGF-beta-induced PAI-1 expression, TGF-beta-induced luciferase reporter gene expression and TGF-beta-induced growth inhibition. Cholesterol, alone or complexed in lipoproteins (LDL, VLDL), suppresses TGF-beta responsiveness by increasing lipid raft and/or caveolae accumulation of TGF-beta receptors and facilitating rapid degradation of TGF-beta and thus suppressing TGF-beta-induced signaling. Conversely, cholesterol-lowering agents (fluvastatin and lovastatin) and cholesterol-depleting agents (beta-cyclodextrin and nystatin) enhance TGF-beta responsiveness by increasing non-lipid raft microdomain accumulation of TGF-beta receptors and facilitating TGF-beta-induced signaling. Furthermore, the effects of cholesterol on the cultured cells are also found in the aortic endothelium of ApoE-null mice fed a high-cholesterol diet. These results suggest that high cholesterol contributes to atherogenesis, at least in part, by suppressing TGF-beta responsiveness in vascular cells.

Links

PubMed PMC2045688 Online version:10.1242/jcs.006916

Keywords

Animals; Aorta; Atherosclerosis/etiology; Atherosclerosis/metabolism; Cattle; Caveolae/metabolism; Cell Cycle Proteins/metabolism; Cell Line; Cholesterol/administration & dosage; Cholesterol/metabolism; Cholesterol/pharmacology; Endothelium, Vascular/metabolism; Epithelial Cells/chemistry; Epithelial Cells/cytology; Epithelial Cells/metabolism; Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology; Lipoproteins, LDL/administration & dosage; Lipoproteins, LDL/metabolism; Membrane Microdomains/metabolism; Mink; Phosphorylation; Plasminogen Activator Inhibitor 1/metabolism; Receptors, Transforming Growth Factor beta/metabolism; Signal Transduction; Smad2 Protein/metabolism; Transforming Growth Factor beta/metabolism; Transforming Growth Factor beta/pharmacology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:TGFB1

enables

GO:0005160: transforming growth factor beta receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q64729

F

Seeded From UniProt

complete

MOUSE:TGFB1

enables

GO:0005160: transforming growth factor beta receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:Q62312

F

Seeded From UniProt

complete

HUMAN:TGFR1

located_in

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:TGFR1

involved_in

GO:0070723: response to cholesterol

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TGFR2

located_in

GO:0005901: caveola

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:TGFR2

located_in

GO:0045121: membrane raft

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:TGFR2

located_in

GO:0005901: caveola

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:TGFR1

located_in

GO:0045121: membrane raft

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:TGFR1

located_in

GO:0005901: caveola

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:TGFR2

located_in

GO:0045121: membrane raft

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:P38438

C

Seeded From UniProt

complete

MOUSE:TGFR2

enables

GO:0005024: transforming growth factor beta-activated receptor activity

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:98728

F

Seeded From UniProt

complete

MOUSE:TGFR2

located_in

GO:0005901: caveola

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:P38438

C

Seeded From UniProt

complete

MOUSE:TGFR2

enables

GO:0050431: transforming growth factor beta binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P04202

F

Seeded From UniProt

complete

MOUSE:TGFR2

involved_in

GO:0070723: response to cholesterol

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TGFR1

located_in

GO:0045121: membrane raft

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:P80204

C

Seeded From UniProt

complete

MOUSE:TGFR1

enables

GO:0005024: transforming growth factor beta-activated receptor activity

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:98729

F

Seeded From UniProt

complete

MOUSE:TGFR1

located_in

GO:0005901: caveola

ECO:0000266: sequence orthology evidence used in manual assertion

UniProtKB:P80204

C

Seeded From UniProt

complete

MOUSE:TGFR1

enables

GO:0050431: transforming growth factor beta binding

ECO:0000353: physical interaction evidence used in manual assertion

PR:P04202

F

Seeded From UniProt

complete

MOUSE:TGFR1

involved_in

GO:0070723: response to cholesterol

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SMAD2

involved_in

GO:0070723: response to cholesterol

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TGFR2

involved_in

GO:0070723: response to cholesterol

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TGFR2

part_of

GO:0005901: caveola

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:TGFR2

involved_in

GO:0042493: response to drug

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TGFB1

involved_in

GO:0070723: response to cholesterol

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TGFB1

involved_in

GO:0032801: receptor catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TGFB1

enables

GO:0005160: transforming growth factor beta receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q64729

F

Seeded From UniProt

complete

MOUSE:TGFB1

enables

GO:0005160: transforming growth factor beta receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q62312

F

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.