原创力文档shear stress modulation of smooth muscle cell marker genes in 2-d and 3-d depends on mechanotransduction by heparan sulfate proteoglycans and erk12剪切应力调制的平滑肌细胞标记基因在2 d和3 d取决于转导硫酸乙酰肝素蛋白聚糖和erk12.pdfVIP
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shear stress modulation of smooth muscle cell marker genes in 2-d and 3-d depends on mechanotransduction by heparan sulfate proteoglycans and erk12剪切应力调制的平滑肌细胞标记基因在2 d和3 d取决于转导硫酸乙酰肝素蛋白聚糖和erk12
Shear Stress Modulation of Smooth Muscle Cell Marker
Genes in 2-D and 3-D Depends on Mechanotransduction
by Heparan Sulfate Proteoglycans and ERK1/2
Zhong-Dong Shi*, Giya Abraham, John M. Tarbell*
Department of Biomedical Engineering, The City College of New York, The City University of New York (CUNY), New York, New York, United States of America
Abstract
Background: During vascular injury, vascular smooth muscle cells (SMCs) and fibroblasts/myofibroblasts (FBs/MFBs) are
exposed to altered luminal blood flow or transmural interstitial flow. We investigate the effects of these two types of fluid
flows on the phenotypes of SMCs and MFBs and the underlying mechanotransduction mechanisms.
Methodology/Principal Findings: Exposure to 8 dyn/cm2 laminar flow shear stress (2-dimensional, 2-D) for 15 h
significantly reduced expression of a-smooth muscle actin (a-SMA), smooth muscle protein 22 (SM22), SM myosin heavy
chain (SM-MHC), smoothelin, and calponin. Cells suspended in collagen gels were exposed to interstitial flow (1 cmH2O,
,0.05 dyn/cm2, 3-D), and after 6 h of exposure, expression of SM-MHC, smoothelin, and calponin were significantly
reduced, while expression of a-SMA and SM22 were markedly enhanced. PD98059 (an ERK1/2 inhibitor) and heparinase III
(an enzyme to cleave heparan sulfate) significantly blocked the effects of laminar flow on gene expression, and also
reversed the effects of interstitial flow on SM-MHC, smoothelin, and calponin, but enhanced interstitial flow-induced
expression of a-SMA and SM22. SMCs and MFBs have similar responses to fluid flow. Silencing ERK1/2 completely blocked
the effects of both laminar flow and interstitial flow on SMC marker gene expression. Western blotting showed that both
types of flows induced ERK1/2 activation that was inh
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