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(Circulation Research. 2006;98:863.)
© 2006 American Heart Association, Inc.

Editorials

Mechanical and Chemical Regulation of Endothelial Cell Polarity

Shu Chien

From the Departments of Bioengineering and Medicine, and Whitaker Institute of Biomedical Engineering, University of California San Diego, La Jolla.

Correspondence to Professor Shu Chien, University of California, San Diego, Department of Bioengineering, PFBH 134, 9500 Gilman Drive, La Jolla, CA 92093-0412. E-mail shuchien@ucsd.edu

See related article, pages 939–946

Key Words: planar cell polarity • endothelial cells • shear stress

An extract of the first 250 words of the full text is provided, because this article has no abstract.

	Introduction

 
McCue et al¹ showed by a combination of in vitro and in vivo studies that shear stress regulates planar cell polarity (PCP) of endothelial cells (ECs) and that glycogen synthase kinase 3ß (GSK3ß) plays a significant role in this process.

	In Vitro Studies on Effects of Shear Stress on PCP and GSK-3ß

 
The application of shear stress at 15 dyn/cm² to cultured porcine aortic ECs caused tubulin acetylation and stabilization of microtubules (MTs), downstream polarization of microtubule-organizing centers (MTOCs), as well as MT orientation and EC elongation in the shear direction. The importance of tubulin dynamics in these shear-induced changes was demonstrated by their elimination by the MT-disrupting agent nocodazole and also the MT-stabilizing agent taxol.

A novel finding is the role of GSK-3ß in shear-induced MT orientation. GSK-3ß is a regulatory serine/threonine kinase² that has high activity under basal state, and its activity is inhibited after serine-9 phosphorylation (p-GSK-3ß); this would lead to downstream signaling³ and MT stabilization,⁴ eg, through the binding of adenomatous polyposis cell protein (APC).^4,5 GSK-3ß can be inhibited by lithium and SB415286, which interfere with the binding of ATP to GSK-3⁶ rather than acting directly on GSK-3 phosphorylation. The evidence that GSK-3ß plays a role in mediating the shear-induced MT orientation and cell shape change is as follows. First, shear stress caused an increase in p-GSK-3ß (at 1 and 4 hours, though waned at 24 hours). Second, inhibition of GSK-3ß by LiCl and SB415286 blocked the shear-induced EC elongation. SB415286 was also shown to reverse the shear-induced downstream localization of MTOCs to become upstream. Third, overexpression . . . [Full Text of this Article]

Related Article:

Shear Stress Regulates Forward and Reverse Planar Cell Polarity of Vascular Endothelium In Vivo and In Vitro

Shannon McCue, Dorota Dajnowiec, Feng Xu, Ming Zhang, Moira R. Jackson, and B. Lowell Langille
Circ. Res. 2006 98: 939-946. [Abstract] [Full Text] [PDF]