Endothelin-1 stimulates contraction and migration of rat pancreatic stellate cells

Atsushi Masamune, Masahiro Satoh, Kazuhiro Kikuta, Noriaki Suzuki, Kennichi Satoh, Tooru Shimosegawa

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)6144-6151
Number of pages8
JournalWorld Journal of Gastroenterology
Volume11
Issue number39
DOIs
Publication statusPublished - 2005 Oct 21

Keywords

  • Endothelin- 1
  • Pancreatic fibrosis
  • Pancreatic stellate cells
  • Pancreatitis
  • Rho kinase

ASJC Scopus subject areas

  • Gastroenterology

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