TY - JOUR
T1 - Endothelin-1 stimulates contraction and migration of rat pancreatic stellate cells
AU - Masamune, Atsushi
AU - Satoh, Masahiro
AU - Kikuta, Kazuhiro
AU - Suzuki, Noriaki
AU - Satoh, Kennichi
AU - Shimosegawa, Tooru
PY - 2005/10/21
Y1 - 2005/10/21
N2 - 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.
AB - 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.
KW - Endothelin- 1
KW - Pancreatic fibrosis
KW - Pancreatic stellate cells
KW - Pancreatitis
KW - Rho kinase
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U2 - 10.3748/wjg.v11.i39.6144
DO - 10.3748/wjg.v11.i39.6144
M3 - Article
C2 - 16273641
AN - SCOPUS:30644469765
VL - 11
SP - 6144
EP - 6151
JO - World Journal of Gastroenterology
JF - World Journal of Gastroenterology
SN - 1007-9327
IS - 39
ER -