Li, YueLi, XuanLiu, JieGuo, WeiZhang, HongchaoWang, Jianchang2017-02-182017Li, Yue, Xuan Li, Jie Liu, Wei Guo, Hongchao Zhang, and Jianchang Wang. 2017. “Enhanced Rb/E2F and TSC/mTOR Pathways Induce Synergistic Inhibition in PDGF-Induced Proliferation in Vascular Smooth Muscle Cells.” PLoS ONE 12 (1): e0170036. doi:10.1371/journal.pone.0170036. http://dx.doi.org/10.1371/journal.pone.0170036.1932-6203http://nrs.harvard.edu/urn-3:HUL.InstRepos:30370989Platelet-derived growth factor (PDGF) plays an essential role in proliferation of vascular smooth muscle cells (VSMCs). The Rb/E2F and TSC/mTOR pathways contribute to the proliferation of VSMCs, but its exact roles in PDGF-induced proliferation are unclear. In this study, we demonstrated the roles of Rb/E2F and TSC/mTOR pathways in PDGF-induced proliferation in VSMCs. We found that PDGF stimulates the activity of E2F and mTOR pathways, and knockdown of either Rb or TSC2 increases PDGF-induced proliferation in VSMCs. More interestingly, we revealed that enhancing both E2F and mTOR activity leads to synergistic inhibition of PDGF-induced proliferation in VSMCs. We further identified that the synergistic inhibition effect is caused by the induced oxidative stress. Summarily, these data suggest the important regulations of Rb/E2F and TSC/mTOR pathways in PDGF-induced proliferation in VSMCs, and also present a promising way to limit deregulated proliferation by PDGF induction in VSMCs.en-USBiology and Life SciencesCell BiologyCell ProcessesCell ProliferationOxidative StressBioassays and physiological analysisBiochemical analysisColorimetric assaysMTT assayEnzyme assaysCell Cycle and Cell DivisionGeneticsGene ExpressionBiochemistryEnzymologyEnzymesOxidoreductasesLuciferaseProteinsCell GrowthBiotechnologyBioengineeringSynthetic BioengineeringGenome EngineeringSynthetic Genome EditingCrisprEngineering and TechnologySynthetic BiologySynthetic GenomicsJournal Article2017-02-1810.1371/journal.pone.0170036