HuR regulates the expression of stress-sensitive genes and mediates inflammatory response in human umbilical vein endothelial cells.
An important aspect of vascular biology is the identification of regulators of stress-sensitive genes that play critical roles in mediating inflammatory response. Here, we show that expression of HuR in human umbilical vein endothelial cells is regulated by shear stress and statin treatment; HuR, in turn, regulates other stress-sensitive genes such as Kruppel-like factor 2 (Klf2), endothelial nitric oxide synthase (eNOS), and bone morphogenic protein 4 (BMP-4). We found that siRNA knockdown of HuR-inhibited inflammatory responses in endothelial cells, including ICAM-1 and VCAM-1 up-regulation, NFkappaB phosphorylation, and adhesion of monocytes. Tissue staining of the mouse aorta revealed increased HuR expression in the lesser curvature region of the arch that is exposed to disturbed flow, consistent with our in vitro data. Taken together, these results suggest that HuR plays a critical role in inducing inflammatory response of endothelial cells under mechanical and biochemical stresses.
Rhee
Won Jong
WJ
Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.
Ni
Chih-Wen
CW
Zheng
Zhilan
Z
Chang
Kyunghwa
K
Jo
Hanjoong
H
Bao
Gang
G
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism / Q000502:physiology*; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D042783:Endothelial Cells / Q000166:cytology*; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D013314:Stress, Mechanical; D014471:Umbilical Veins / Q000166:cytology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D000954:Antigens, Surface; D055415:Bone Morphogenetic Protein 4; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; D016328:NF-kappa B; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D052250:Nitric Oxide Synthase Type III