Hepatic stimulator substance alleviates toxin-induced and immune-mediated liver injury and fibrosis in rats.

Abstract

BACKGROUND:

Liver fibrosis is a common scarring response to chronic liver injury. It is a precursor to cirrhosis and liver carcinoma. Hepatic stimulator substance (HSS), a known liver-specific but species-nonspecific growth factor, has been shown to protect hepatocytes from various toxins.

METHODS:

We have investigated the effects of HSS therapy on carbon tetrachloride (CCl(4))-induced and porcine-serum-mediated hepatic injury and fibrosis. We hypothesize that HSS might attenuate liver injury and fibrosis by suppressing oxidative stress, down-regulating profibrogenic factors, and blocking HSCs activation.

RESULTS:

This report demonstrated that HSS therapy diminished α-smooth muscle actin expression, decreased intrahepatic reactive oxygen species (ROS) level, and down-regulated transforming growth factor (TGF)-β1, platelet-derived growth factor (PDGF)-BB, and tissue inhibitor of metalloproteinase (TIMP)-1 expression. In addition, HSS treatment significantly protected the liver from injury by improving liver function tests and histological architecture of the liver.

CONCLUSIONS:

These results provided novel insights into the mechanisms of HSS in the protection of the liver. Our results suggested that HSS might be a therapeutic antifibrotic agent for the treatment of liver fibrosis.

• Authors: Xuerui Yi, Ming Song, Youcheng Yuan, Xinrui Zhang, Wenyin Chen, Jin Li, Minghua Tong, Guangze Liu, Song You, Xiangping Kong
• Journal: Digestive diseases and sciences (Dig Dis Sci) Vol. 57 Issue 8 Pg. 2079-87 (Aug 2012) ISSN: 1573-2568 [Electronic] United States
• PMID: 22539040 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Intercellular Signaling Peptides and Proteins
• Mitogens
• Peptides
• Proto-Oncogene Proteins c-sis
• Reactive Oxygen Species
• Tissue Inhibitor of Metalloproteinase-1
• Transforming Growth Factor beta1
• hepatic stimulator substance
• Becaplermin

Topics

• Animals
• Becaplermin
• Carbon Tetrachloride Poisoning (drug therapy)
• Chemical and Drug Induced Liver Injury (drug therapy)
• Hepatic Stellate Cells (drug effects)
• Intercellular Signaling Peptides and Proteins
• Liver (metabolism)
• Liver Cirrhosis (drug therapy, metabolism)
• Liver Function Tests
• Male
• Mitogens (pharmacology, therapeutic use)
• Oxidative Stress (drug effects)
• Peptides (pharmacology, therapeutic use)
• Proto-Oncogene Proteins c-sis (metabolism)
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Swine
• Tissue Inhibitor of Metalloproteinase-1 (metabolism)
• Transforming Growth Factor beta1 (metabolism)