HuR regulates the expression of stress-sensitive genes and mediates inflammatory response in human umbilical vein endothelial cells

Citation:

Rhee WJ, Ni CW, Zheng Z, Chang K, Jo H, Bao G. HuR regulates the expression of stress-sensitive genes and mediates inflammatory response in human umbilical vein endothelial cells. Proc Natl Acad Sci U S A 2010;107:6858-63.

Abstract:

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.

Notes:

Rhee, Won JongNi, Chih-WenZheng, ZhilanChang, KyunghwaJo, HanjoongBao, GangengCA119338/CA/NCI NIH HHS/HL70531/HL/NHLBI NIH HHS/HL80711/HL/NHLBI NIH HHS/Research Support, N.I.H., Extramural2010/03/31 06:00Proc Natl Acad Sci U S A. 2010 Apr 13;107(15):6858-63. doi: 10.1073/pnas.1000444107. Epub 2010 Mar 29.