title: Enhanced Rb/E2F and TSC/mTOR Pathways Induce Synergistic Inhibition in PDGF-Induced Proliferation in Vascular Smooth Muscle Cells.
abstract: Platelet-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.
authors.affiliation: Department of Cardiac surgery, Air Force General Hospital of People`s Liberation Army, Beijing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Vascular and Thyroid Surgery, 1st Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Vascular and Endovascular Surgery, General Hospital of People`s Liberation Army, Beijing, China.|Vascular Surgery Research Laboratories, Division of Vascular and Endovascular Suregery, Brigham and Woman's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Vascular and Endovascular Surgery, General Hospital of People`s Liberation Army, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Cardiac surgery, Air Force General Hospital of People`s Liberation Army, Beijing, China.
authors.forename: Hongchao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Cardiac surgery, Air Force General Hospital of People`s Liberation Army, Beijing, China.
authors.forename: Jianchang
authors.initials: J
authors.lastname: Wang
mesh_terms: D002135:Calcium-Binding Proteins / Q000378:metabolism / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D050684:E2F Transcription Factors / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D016160:Retinoblastoma Protein / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D002135:Calcium-Binding Proteins; D050684:E2F Transcription Factors; D010982:Platelet-Derived Growth Factor; D016160:Retinoblastoma Protein; C486009:TESC protein, human; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases