CCN1 expression in hepatocytes contributes to macrophage infiltration in nonalcoholic fatty liver disease in mice[S]

Our objective was to investigate the potential roles of CCN1 in the inflammation and macrophage infiltration of nonalcoholic fatty liver disease (NAFLD). The regulation of hepatic CCN1 expression was investigated in vitro with murine primary hepatocytes treated with free fatty acids or lipopolysacch...

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Main Authors: Zhaolian Bian, Yanshen Peng, Zhengrui You, Qixia Wang, Qi Miao, Yuan Liu, Xiaofeng Han, Dekai Qiu, Zhiping Li, Xiong Ma
Format: Article
Language:English
Published: Elsevier 2013-01-01
Series:Journal of Lipid Research
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520417602
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author Zhaolian Bian
Yanshen Peng
Zhengrui You
Qixia Wang
Qi Miao
Yuan Liu
Xiaofeng Han
Dekai Qiu
Zhiping Li
Xiong Ma
author_facet Zhaolian Bian
Yanshen Peng
Zhengrui You
Qixia Wang
Qi Miao
Yuan Liu
Xiaofeng Han
Dekai Qiu
Zhiping Li
Xiong Ma
author_sort Zhaolian Bian
collection DOAJ
description Our objective was to investigate the potential roles of CCN1 in the inflammation and macrophage infiltration of nonalcoholic fatty liver disease (NAFLD). The regulation of hepatic CCN1 expression was investigated in vitro with murine primary hepatocytes treated with free fatty acids or lipopolysaccharide (LPS) and in vivo with high-fat (HF) diet-fed mice or ob/ob mice. CCN1 protein and a liver-specific CCN1 expression plasmid were administered to mice fed a normal diet (ND) or HF diet. Myeloid-derived macrophages and RAW264.7 cells were also treated with CCN1 in vitro to determine the chemotactic effects of CCN1 on macrophages. LPS treatment significantly increased hepatic CCN1 expression in HF diet-fed mice and ob/ob mice. LPS and FFAs induced CCN1 expression in primary murine hepatocytes in vitro through the TLR4/MyD88/AP-1 pathway. CCN1 protein and overexpression of CCN1 in the liver induced more severe hepatic inflammation and macrophage infiltrates in HF mice than in ND mice. CCN1 recruited macrophages through activation of the Mek/Erk signaling pathway in myeloid-derived macrophages and RAW264.7 cells in vitro. Endotoxin and FFA-induced CCN1 expression in hepatocytes is involved in the hepatic proinflammatory response and macrophage infiltration in murine NAFLD.
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spelling doaj.art-a16454737604457c98a2e5bd71cf4a662022-12-21T19:58:23ZengElsevierJournal of Lipid Research0022-22752013-01-015414454CCN1 expression in hepatocytes contributes to macrophage infiltration in nonalcoholic fatty liver disease in mice[S]Zhaolian Bian0Yanshen Peng1Zhengrui You2Qixia Wang3Qi Miao4Yuan Liu5Xiaofeng Han6Dekai Qiu7Zhiping Li8Xiong Ma9Division of Gastroenterology and Hepatology, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai, China; Shanghai Institute of Digestive Disease; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health (Shanghai Jiao-Tong University), Shanghai, China; andDivision of Gastroenterology and Hepatology, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai, China; Shanghai Institute of Digestive Disease; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health (Shanghai Jiao-Tong University), Shanghai, China; andDivision of Gastroenterology and Hepatology, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai, China; Shanghai Institute of Digestive Disease; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health (Shanghai Jiao-Tong University), Shanghai, China; andDivision of Gastroenterology and Hepatology, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai, China; Shanghai Institute of Digestive Disease; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health (Shanghai Jiao-Tong University), Shanghai, China; andDivision of Gastroenterology and Hepatology, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai, China; Shanghai Institute of Digestive Disease; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health (Shanghai Jiao-Tong University), Shanghai, China; andDivision of Gastroenterology and Hepatology, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai, China; Shanghai Institute of Digestive Disease; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health (Shanghai Jiao-Tong University), Shanghai, China; andDivision of Gastroenterology and Hepatology, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai, China; Shanghai Institute of Digestive Disease; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health (Shanghai Jiao-Tong University), Shanghai, China; andDivision of Gastroenterology and Hepatology, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai, China; Shanghai Institute of Digestive Disease; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health (Shanghai Jiao-Tong University), Shanghai, China; andDepartment of Medicine, Johns Hopkins University, Baltimore, MDTo whom correspondence should be addressed. e-mail: maxiongmd@hotmail.com.; Division of Gastroenterology and Hepatology, Shanghai Jiao-Tong University School of Medicine Renji Hospital, Shanghai, China; Shanghai Institute of Digestive Disease; Key Laboratory of Gastroenterology & Hepatology, Ministry of Health (Shanghai Jiao-Tong University), Shanghai, China; and; To whom correspondence should be addressed. e-mail: maxiongmd@hotmail.com.Our objective was to investigate the potential roles of CCN1 in the inflammation and macrophage infiltration of nonalcoholic fatty liver disease (NAFLD). The regulation of hepatic CCN1 expression was investigated in vitro with murine primary hepatocytes treated with free fatty acids or lipopolysaccharide (LPS) and in vivo with high-fat (HF) diet-fed mice or ob/ob mice. CCN1 protein and a liver-specific CCN1 expression plasmid were administered to mice fed a normal diet (ND) or HF diet. Myeloid-derived macrophages and RAW264.7 cells were also treated with CCN1 in vitro to determine the chemotactic effects of CCN1 on macrophages. LPS treatment significantly increased hepatic CCN1 expression in HF diet-fed mice and ob/ob mice. LPS and FFAs induced CCN1 expression in primary murine hepatocytes in vitro through the TLR4/MyD88/AP-1 pathway. CCN1 protein and overexpression of CCN1 in the liver induced more severe hepatic inflammation and macrophage infiltrates in HF mice than in ND mice. CCN1 recruited macrophages through activation of the Mek/Erk signaling pathway in myeloid-derived macrophages and RAW264.7 cells in vitro. Endotoxin and FFA-induced CCN1 expression in hepatocytes is involved in the hepatic proinflammatory response and macrophage infiltration in murine NAFLD.http://www.sciencedirect.com/science/article/pii/S0022227520417602cell signalingcytokinesdiet and dietary lipidsfatty acidCyr61chemotaxis
spellingShingle Zhaolian Bian
Yanshen Peng
Zhengrui You
Qixia Wang
Qi Miao
Yuan Liu
Xiaofeng Han
Dekai Qiu
Zhiping Li
Xiong Ma
CCN1 expression in hepatocytes contributes to macrophage infiltration in nonalcoholic fatty liver disease in mice[S]
Journal of Lipid Research
cell signaling
cytokines
diet and dietary lipids
fatty acid
Cyr61
chemotaxis
title CCN1 expression in hepatocytes contributes to macrophage infiltration in nonalcoholic fatty liver disease in mice[S]
title_full CCN1 expression in hepatocytes contributes to macrophage infiltration in nonalcoholic fatty liver disease in mice[S]
title_fullStr CCN1 expression in hepatocytes contributes to macrophage infiltration in nonalcoholic fatty liver disease in mice[S]
title_full_unstemmed CCN1 expression in hepatocytes contributes to macrophage infiltration in nonalcoholic fatty liver disease in mice[S]
title_short CCN1 expression in hepatocytes contributes to macrophage infiltration in nonalcoholic fatty liver disease in mice[S]
title_sort ccn1 expression in hepatocytes contributes to macrophage infiltration in nonalcoholic fatty liver disease in mice s
topic cell signaling
cytokines
diet and dietary lipids
fatty acid
Cyr61
chemotaxis
url http://www.sciencedirect.com/science/article/pii/S0022227520417602
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