title: Rosiglitazone attenuates angiotensin II-induced C-reactive protein expression in hepatocytes via inhibiting AT1/ROS/MAPK signal pathway.
abstract: Inflammation is a commonly pathological change in liver diseases, and promotes the development of acute and chronic liver diseases by excessive production of inflammatory cytokines. C-reactive protein (CRP) is primarily synthesized in the liver and participates in many chronic diseases. Our previous study confirmed that Ang II stimulates CRP generation in hepatocytes. This study investigated the effect of rosiglitazone (RSG) on Ang II-stimulated CRP expression and the molecular mechanism in hepatocytes. The results showed that the subcutaneous infusion of Ang II to rats for 7days through the osmotic minipumps increased CRP expression in the liver and serum CRP level. The simultaneous treatment of rats with RSG reduced CRP generation in the liver and CRP concentration in serum. Further study showed that RSG down-regulated Ang II-induced mRNA and protein expression of CRP and AT1 as well as phosphorylation of ERK1/2 and JNK, enhanced mRNA and protein expression of PPARγ in hepatocytes in vivo and in vitro. In addition, RSG increased superoxide dismutase activity in the liver of Ang II-infused rats in vivo, and decreased Ang II-stimulated reactive oxygen species (ROS) production in hepatocytes in vitro. In conclusion, the present study demonstrates that RSG is able to inhibit Ang II-induced CRP generation by interfering with AT1-ROS-ERK1/2/JNK signal pathway and up-regulating PPARγ expression in hepatocytes, which provides the new evidence and mechanisms for the beneficial effect of RSG to relieve hepatic inflammation and suggests the possibility that RSG is used for the inflammatory hepatic diseases.
authors.affiliation: Translational Medicine Center, Hong Hui Hospital, Xi'an Jiaotong University School of Medicine, Xi'an 710054, China. Electronic address: jjzhao86@163.com.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China. Electronic address: ljt@xjtu.edu.cn.
authors.forename: Juntian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Pang
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.
authors.forename: Shuyue
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage; D000818:Animals; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006505:Hepatitis / Q000188:drug therapy*; D022781:Hepatocytes / Q000187:drug effects* / Q000502:physiology; D008297:Male; D047495:PPAR gamma / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D000077154:Rosiglitazone; D015398:Signal Transduction / Q000187:drug effects; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: C544067:Agtr1a protein, rat; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000804:Angiotensin II; D002097:C-Reactive Protein; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Angiotensin II; C-reactive protein; Hepatocytes; Inflammation; Rosiglitazone