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Different profiles of Ca 2+ responses to endothelin‐1 and PDGF in liver myofibroblasts during the process of cell differentiation
Author(s) -
Kojima N,
Hori M,
Murata T,
Morizane Y,
Ozaki H
Publication year - 2007
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0707269
Subject(s) - hepatic stellate cell , platelet derived growth factor receptor , myofibroblast , extracellular , intracellular , platelet derived growth factor , biology , chemistry , growth factor , microbiology and biotechnology , endocrinology , medicine , receptor , fibrosis , biochemistry
Background and purpose: Hepatic stellate cells play an important role in liver fibrosis but little is known about liver myofibroblasts located around the central vein and in the portal area. In this study, intracellular Ca 2+ concentration ([Ca 2+ ] i ) was measured to assess the response to endothelin‐1 (ET‐1), platelet derived growth factor (PDGF) and ATP in rat liver myofibroblasts. Experimental approach: Rat liver myofibroblasts were compared in ‘quiescent’ (cultured on Matrigel‐coated dishes) and ‘activated’ (cultured on non‐coated plastic dishes) conditions. [Ca 2+ ] i was measured with the fluorescent dye fura‐2 and mRNA for ET‐1, PDGF and their receptors by RT‐PCR. Key results: ET‐1 increased [Ca 2+ ] i in quiescent cells but not in activated cells, whereas PDGF‐BB increased [Ca 2+ ] i in activated cells but not in quiescent cells. However, there was no difference between responses to ATP in quiescent or activated cells. ET‐1 (in quiescent cells), PDGF‐BB (in activated cells) and ATP (in both cells) all induced transient increases in [Ca 2+ ] i in the absence of extracellular Ca 2+ (with EGTA), indicating the involvement of Ca 2+ release from intracellular Ca 2+ stores. The sustained increase in [Ca 2+ ] i in the presence of external Ca 2+ in activated cells (ATP and PDGF) was significantly reduced by nicardipine, a L‐type Ca 2+ channel blocker, but not in quiescent cells (ATP and ET‐1). Conclusions and implications: The different pharmacological profiles of [Ca 2+ ] i ‐response in quiescent and activated myofibroblasts suggest that ET‐1 and PDGF contribute differently to myofibroblast activation during the process of liver fibrosis. British Journal of Pharmacology (2007) 151 , 816–827; doi: 10.1038/sj.bjp.0707269