Protecting effects of vasonatrin peptide against carbon tetrachloride-induced liver fibrosis.

Abstract

In order to investigate the effects of vasonatrin peptide (VNP), a novel man-made natriuretic peptide, on liver fibrosis, mice received carbon tetrachloride (CCl(4)) injection for 12weeks and with or without VNP treatment during the last 6weeks. Hematoxylin-eosin (HE) staining and Sirius red staining were performed to evaluate the status of liver fibrosis. After treatment of VNP, DNA and collagen synthesis of cultured HSC-T6 hepatic stellate cells were assessed by [(3)H]-thymidine and [(3)H]-proline incorporation, respectively. Additionally, involved signaling pathway was identified by radioimmunoassay to detect the levels of intracellular cGMP and by mimicking experiments using 8-br-cGMP (a membrane-permeable cGMP analog). Also, blocking experiments were performed using HS-142-1, an antagonist of guanylyl cyclase-coupled natriuretic peptide receptor (NPR), or KT-5823, the cGMP-dependent protein kinase (PKG) inhibitor. As a result, VNP markedly alleviated CCl(4)-induced liver fibrosis in mice. In vitro, HSC-T6 cells demonstrated a dose-dependent reduction of DNA and collagen synthesis in the presence VNP. In addition, VNP significantly increased the intracellular levels of cGMP. These effects of VNP were mimicked by 8-br-cGMP, although inhibited by HS-142-1 or KT-5823. Taken together, VNP ameliorates liver fibrosis by inhibiting collagen production from hepatic stellate cells via guanylyl cyclase-coupled NPR/cGMP/PKG pathway, indicating that VNP might be a new effective reagent in the treatment of liver fibrosis.

• Authors: Bao-Ying Chen, Ping Qu, Ru Tie, Miao-Zhang Zhu, Xiao-Xing Zhu, Jun Yu
• Journal: Regulatory peptides (Regul Pept) Vol. 164 Issue 2-3 Pg. 139-43 (Sep 24 2010) ISSN: 1873-1686 [Electronic] Netherlands
• PMID: 20619296 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier B.V. All rights reserved.

Chemical References

• Carbazoles
• Protein Kinase Inhibitors
• KT 5823
• ventricular natriuretic peptide, eel
• Atrial Natriuretic Factor
• Collagen
• Carbon Tetrachloride
• Cyclic GMP-Dependent Protein Kinases
• Cyclic GMP

Topics

• Animals
• Atrial Natriuretic Factor (pharmacology, therapeutic use)
• Carbazoles (pharmacology)
• Carbon Tetrachloride (toxicity)
• Cell Line
• Collagen (metabolism)
• Cyclic GMP (metabolism)
• Cyclic GMP-Dependent Protein Kinases (antagonists & inhibitors, metabolism)
• Hepatic Stellate Cells (drug effects, metabolism)
• Liver Cirrhosis (chemically induced, drug therapy)
• Male
• Mice
• Mice, Inbred BALB C
• Protein Kinase Inhibitors (pharmacology)
• Rats