HMG-CoA reductase inhibitor simvastatin mitigates VEGF-induced “inside-out” signaling to extracellular matrix by preventing RhoA activation
Xu H, Zeng L, Peng H, Chen S, Jones J, Chew TL, Sadeghi MM, Kanwar YS, Danesh FR. HMG-CoA reductase inhibitor simvastatin mitigates VEGF-induced “inside-out” signaling to extracellular matrix by preventing RhoA activation. American Journal Of Physiology. Renal Physiology 2006, 291: f995-f1004. PMID: 16774905, DOI: 10.1152/ajprenal.00092.2006.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonActinsAnimalsCells, CulturedCollagen Type IVExtracellular MatrixFocal Adhesion Protein-Tyrosine KinasesHydroxymethylglutaryl-CoA Reductase InhibitorsIntegrin beta1Mesangial CellsMevalonic AcidPhosphorylationProlineRatsRhoA GTP-Binding ProteinSignal TransductionSimvastatinTritiumTyrosineVascular Endothelial Growth Factor AConceptsRhoA activationIntact actin cytoskeletonCell signaling cascadesPrecise signaling mechanismUnderlying molecular mechanismsActin cytoskeletonECM expansionMevalonate depletionSignaling cascadesIntegrin activationMevalonate pathwayECM accumulationMolecular mechanismsVEGF stimulationSignaling mechanismComplex biologyExtracellular matrixPleiotropic effectsAngiogenic polypeptideType IV collagen accumulationEndothelial cell permeabilityExtracellular matrix accumulationCell permeabilityGrowth factorPathological processes