Basic Research
Copyright ©The Author(s) 2005. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 21, 2005; 11(39): 6144-6151
Published online Oct 21, 2005. doi: 10.3748/wjg.v11.i39.6144
Endothelin-1 stimulates contraction and migration of rat pancreatic stellate cells
Atsushi Masamune, Masahiro Satoh, Kazuhiro Kikuta, Noriaki Suzuki, Kennichi Satoh, Tooru Shimosegawa
Atsushi Masamune, Masahiro Satoh, Kazuhiro Kikuta, Noriaki Suzuki, Kennichi Satoh, Tooru Shimosegawa, Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
Author contributions: All authors contributed equally to the work.
Supported by Grant-in-Aid for Encouragement of Young Scientists from Japan Society for the Promotion of Science, No. 16590572 (to AM.), by Pancreas Research Foundation of Japan, No. 01-01 (to AM.), by the Kanae Foundation for Life and Socio-Medical Science (to AM), and by the Uehara Memorial Foundation (to AM)}
Correspondence to: Dr. Atsushi Masamune, Division of Gastro-enterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574,Japan.amasamune@int3.med.tohoku.ac.jp
Telephone: +81-22-717-7171 Fax: +81-22-717-7177
Received: December 19, 2004
Revised: February 15, 2005
Accepted: February 18, 2005
Published online: October 21, 2005
Abstract

AIM: To examine the ability of ET-1 to affect the cell functions of PSCs and the underlying molecular mechanisms.

METHODS: PSCs were isolated from the pancreas of male Wistar rats after perfusion with collagenase, and cells between passages two and five were used. Expression of ET-1 and ET receptors was assessed by reverse transcription-PCR and immunostaining. Phosphorylation of myosin regulatory light chain (MLC), extracellular-signal regulated kinase (ERK), and Akt was examined by Western blotting. Contraction of PSCs was assessed on hydrated collagen lattices. Cell migration was examined using modified Boyden chambers. Cell proliferation was assessed by measuring the incorporation of 5-bromo-2×deoxyuridine.

RESULTS: Culture-activated PSCs expressed ETA and ETB receptors, and ET-1. ET-1 induced phosphorylation of MLC and ERK, but not Akt. ET-1 induced contraction and migration, but did not alter proliferation of PSCs. ET-1-induced contraction was inhibited by an ETA receptor antagonist BQ-123 and an ETB receptor antagonist BQ-788, whereas migration was inhibited by BQ-788 but not by BQ-123. A Rho kinase inhibitor Y-27632 abolished both contraction and migration.

CONCLUSION: ET-1 induced contraction and migration of PSCs through ET receptors and activation of Rho-Rho kinase. ETA and ETB receptors play different roles in the regulation of these cellular functions in response to ET-1.

Keywords: Pancreatitis; Pancreatic fibrosis; Pancreatic stellate cells; Endothelin-1; Rho kinase