Park KS, Sin PJ, Lee DH, Cha SK, Kim MJ, Kim NH, Baik SK, Jeong SW, Kong ID. Switching-on of serotonergic calcium signaling in activated hepatic stellate cells. World J Gastroenterol 2011; 17(2): 164-173 [PMID: 21245988 DOI: 10.3748/wjg.v17.i2.164]
Corresponding Author of This Article
In Deok Kong, Professor, Department of Physiology and Institute of Lifelong Health, Yonsei University Wonju College of Medicine, 162 Ilsan-Dong, Wonju, Gangwon-Do, 220-701, South Korea. kong@yonsei.ac.kr
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Park KS, Sin PJ, Lee DH, Cha SK, Kim MJ, Kim NH, Baik SK, Jeong SW, Kong ID. Switching-on of serotonergic calcium signaling in activated hepatic stellate cells. World J Gastroenterol 2011; 17(2): 164-173 [PMID: 21245988 DOI: 10.3748/wjg.v17.i2.164]
World J Gastroenterol. Jan 14, 2011; 17(2): 164-173 Published online Jan 14, 2011. doi: 10.3748/wjg.v17.i2.164
Switching-on of serotonergic calcium signaling in activated hepatic stellate cells
Kyu-Sang Park, Pyo-Jin Sin, Dong Hyeon Lee, Seung-Kuy Cha, Min-Jeong Kim, Na-Hyun Kim, Soon-Koo Baik, Seong-Woo Jeong, In Deok Kong
Kyu-Sang Park, Pyo-Jin Sin, Seung-Kuy Cha, Min-Jeong Kim, Seong-Woo Jeong, In Deok Kong, Department of Physiology and Institute of Lifelong Health, Yonsei University Wonju College of Medicine, Wonju, Gangwon-Do, 220-701, South Korea
Dong Hyeon Lee, Department of Physiology, College of Medicine, Pochon CHA University, Seongnam, Gyeonggi-Do, 463-712, South Korea
Na-Hyun Kim, Department of Basic Nursing Science, Keimyung University College of Nursing, Daegu, 700-712, South Korea
Soon-Koo Baik, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Gangwon-Do, 220-701, South Korea
Author contributions: Park KS, Sin PJ and Kong ID designed the project; Park KS, Sin PJ, Lee DH, Cha SK, Kim MJ and Kim NH performed the experiments; Park KS, Sin PJ and Kong ID wrote the manuscript; Baik SK and Jeong SW contributed to the discussion of the data and the revision of the manuscript.
Supported by Grants from the Korean National Research Foundation (2010-0014617); the Myung Sun Kim Memorial Foundation (2009); and the Yonsei University Faculty Research Grant (2004)
Correspondence to: In Deok Kong, Professor, Department of Physiology and Institute of Lifelong Health, Yonsei University Wonju College of Medicine, 162 Ilsan-Dong, Wonju, Gangwon-Do, 220-701, South Korea. kong@yonsei.ac.kr
Telephone: +82-33-7410292 Fax: +82-33-7456461
Received: September 6, 2010 Revised: October 11, 2010 Accepted: October 18, 2010 Published online: January 14, 2011
Abstract
AIM: To investigate serotonergic Ca2+ signaling and the expression of 5-hydroxytryptamine (5-HT) receptors, as well as Ca2+ transporting proteins, in hepatic stellate cells (HSCs).
METHODS: The intracellular Ca2+ concentration ([Ca2+]i) of isolated rat HSCs was measured with a fluorescence microscopic imaging system. Quantitative PCR was performed to determine the transcriptional levels of 5-HT receptors and endoplasmic reticulum (ER) proteins involved in Ca2+ storage and release in cultured rat HSCs.
RESULTS: Distinct from quiescent cells, activated HSCs exhibited [Ca2+]i transients following treatment with 5-HT, which was abolished by U-73122, a phospholipase C inhibitor. Upregulation of 5-HT2A and 5-HT2B receptors, but not 5-HT3, was prominent during trans-differentiation of HSCs. Pretreatment with ritanserin, a 5-HT2 antagonist, inhibited [Ca2+]i changes upon application of 5-HT. Expression of type 1 inositol-5’-triphosphate receptor and type 2 sarcoplasmic/endoplasmic reticulum Ca2+ ATPase were also increased during activation of HSCs and serve as the major isotypes for ER Ca2+ storage and release in activated HSCs. Ca2+ binding chaperone proteins of the ER, including calreticulin, calnexin and calsequestrin, were up-regulated following activation of HSCs.
CONCLUSION: The appearance of 5-HT-induced [Ca2+]i response accompanied by upregulation of metabotropic 5-HT2 receptors and Ca2+ transporting/chaperone ER proteins may participate in the activating process of HSCs.
