PDGF-BB and TGF-β1 on cross-talk between endothelial and smooth muscle cells in vascular remodeling induced by low shear stress

被引:146
作者
Qi, Ying-Xin [1 ]
Jiang, Jun [1 ]
Jiang, Xiao-Hua [1 ]
Wang, Xiao-Dong [1 ]
Ji, Su-Ying [1 ]
Han, Yue [1 ]
Long, Ding-Kun [1 ]
Shen, Bao-Rong [1 ]
Yan, Zhi-Qiang [1 ]
Chien, Shu [2 ,3 ,4 ]
Jiang, Zong-Lai [1 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Life Sci & Biotechnol, Inst Mechanobiol & Med Engn, Shanghai 200240, Peoples R China
[2] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA
[3] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA
[4] Univ Calif San Diego, Inst Engn Med, La Jolla, CA 92093 USA
基金
中国国家自然科学基金;
关键词
mechanotransduction; mechanobiology; bioinformatics; cell biology; LYSYL OXIDASE; MIGRATION; EXPRESSION; COCULTURE; MECHANICS; BIOLOGY;
D O I
10.1073/pnas.1019219108
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Shear stress, especially low shear stress (LowSS), plays an important role in vascular remodeling during atherosclerosis. Endothelial cells (ECs), which are directly exposed to shear stress, convert mechanical stimuli into intracellular signals and interact with the underlying vascular smooth muscle cells (VSMCs). The interactions between ECs and VSMCs modulate the LowSS-induced vascular remodeling. With the use of proteomic analysis, the protein profiles of rat aorta cultured under LowSS (5 dyn/cm(2)) and normal shear stress (15 dyn/cm(2)) were compared. By using Ingenuity Pathway Analysis to identify protein-protein association, a network was disclosed that involves two secretary molecules, PDGF-BB and TGF-beta 1, and three other linked proteins, lamin A, lysyl oxidase, and ERK 1/2. The roles of this network in cellular communication, migration, and proliferation were further studied in vitro by a cocultured parallel-plate flow chamber system. LowSS up-regulated migration and proliferation of ECs and VSMCs, increased productions of PDGF-BB and TGF-beta 1, enhanced expressions of lysyl oxidase and phospho-ERK1/2, and decreased Lamin A in ECs and VSMCs. These changes induced by LowSS were confirmed by using PDGF-BB recombinant protein, siRNA, and neutralizing antibody. TGF-beta 1 had similar influences on ECs as PDGF-BB, but not on VSMCs. Our results suggest that ECs convert the LowSS stimuli into up-regulations of PDGF-BB and TGF-beta 1, but these two factors play different roles in LowSS-induced vascular remodeling. PDGF-BB is involved in the paracrine control of VSMCs by ECs, whereas TGF-beta 1 participates in the feedback control from VSMCs to ECs.
引用
收藏
页码:1908 / 1913
页数:6
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