title: Positive feedback regulation of proliferation in vascular smooth muscle cells stimulated by lipopolysaccharide is mediated through the TLR 4/Rac1/Akt pathway.
abstract: Toll-like receptor 4 (TLR4) are important in inflammation and regulating vascular smooth muscle cells (VSMCs) proliferation, which are related to atherosclerosis and restenosis. We have investigated the mechanisms involved in Lipopolysaccharide (LPS)-induced proliferation of VSMCs. Stimulation of rat aortic VSMCs with LPS significantly increases the proliferation of VSMCs. This effect is regulated by Rac1 (Ras-related C3 botulinum toxin substrate l), which mediates the activation of phosphatidylinositol 3-kinase/Akt (PI3K/Akt) signaling pathways. Inhibition of Rac1 activity by NSC23766 is associated with inhibition of Akt activity. Treatment with NSC23766 or LY294002 significantly decreases LPS-induced TLR4 protein and mRNA expression. The data show that positive feedback regulation of proliferation in VSMCs is mediated through the TLR4/Rac1/Akt pathway.
authors.affiliation: Institute of Cardiovascular Disease Research, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Dehua
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Institute of Cardiovascular Disease Research, Xuzhou Medical College, Xuzhou, Jiangsu, China; Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Dongye
authors.initials: D
authors.lastname: Li
authors.affiliation: Institute of Cardiovascular Disease Research, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Cao
authors.affiliation: Institute of Cardiovascular Disease Research, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Lele
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Cardiovascular Disease Research, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Tongda
authors.initials: T
authors.lastname: Xu
authors.affiliation: Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Defeng
authors.initials: D
authors.lastname: Pan
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D047468:Immunoprecipitation; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D012333:RNA, Messenger; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein