Activation of PAR₄ Induces a Distinct Actin Fiber Formation via p38 MAPK in Human Lung Endothelial Cells

Masakazu Fujiwara ¹, Enjing Jin ¹, Mohammad Ghazizadeh ¹ and Oichi Kawanami ^1*

¹ Department of Molecular Pathology, Nippon Medical School, Graduate School of Medicine, Institute of Gerontology, Kanagawa, Japan

^* To whom correspondence should be addressed. E-mail: E-mail: kawanami{at}nms.ac.jp.

Submitted on December 2, 2004
Accepted on 23 March 2005

	Abstract

Protease-activated receptors (PARs) are multi-functional G protein coupled receptors. Among the four existing PARs, PAR₄ is preferentially expressed in the human lung tissue. However, the function of PAR₄ has not been defined in the lung endothelial cells. Since PAR₁-mediated cellular effects are deeply related to the morphological changes, we focused on the actin fiber and p38 MAPK signaling involved in actin polymerization to elucidate the role of PAR₄. RT-PCR and Western blot analyses identified PAR₄ expression in human pulmonary artery endothelial cells (HPAEC) and in human microvascular endothelial cells from lung (HMVEC-L). We then examined the changes in actin fibers in endothelial cells treated with PAR₄ activating peptide (GYPGQV). PAR₁ activating peptide (SFLLRN) was used for comparison. Activation of PAR₄ and PAR₁ by their corresponding peptides induced actin fiber formation, however, the actin filaments were broadly bundled in PAR₄ as compared with the ring like actin filaments in PAR₁ activation. Correspondingly, the magnitude of p38 MAPK phosphorylation was different between cells treated with PAR₄ and PAR₁, with PAR₄ activating peptide showing a significantly higher sensitivity to p38 MAPK inhibitor, SB203580. Taken together, these results demonstrate that activation of PAR₄ results in the formation of actin fiber distinct from that by PAR₁ activation, suggesting PAR₄ may play specific roles in the lung endothelial cells.

Key Words: pulmonary endothelial cells, G-protein coupled receptors, protease-activated receptor, thrombin, actin; p38 MAPK

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				A. J. Leger, L. Covic, and A. Kuliopulos Protease-Activated Receptors in Cardiovascular Diseases Circulation, September 5, 2006; 114(10): 1070 - 1077. [Abstract] [Full Text] [PDF]

Guidelines | Subscriptions | About | exPRESS - Current - Archive | Business Information | Contact

The Journal of Histochemistry & Cytochemistry is owned, published, and licensed by The Histochemical Society © 2005