Augmenter of liver regeneration (ALR) gene therapy attenuates CCl₄-induced liver injury and fibrosis in rats.
Liver fibrosis represents a process of healing and scarring in response to chronic liver injury. Augmenter of liver regeneration (ALR) has been shown to protect hepatocytes from various toxins. The aim of this study was to investigate the effects of ALR gene therapy on liver injury and fibrosis induced by CCl(4) in rats and further explore the underlying mechanisms. Human ALR expression plasmid was delivered via the tail vein. ALR gene therapy might protect the liver from CCl(4)-induced injury and fibrogenesis by attenuating the mitochondrial dysfunction, suppressing oxidative stress, and inhibiting activation of HSCs. This report demonstrated that ALR gene therapy protected against the ATP loss, increased the activity of ATPase, decreased intrahepatic reactive oxygen species level, and down-regulated transforming growth factor-β1, platelet-derived growth factor-BB, and α-smooth muscle actin expression. Following gene transfer liver function tests were significantly improved. In brief, ALR gene therapy might be an effective therapeutic reagent for liver fibrosis with potential clinical applications.
Institute of Life Science and Bio-pharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
Ming
M
Song
Xuerui
X
Yi
Wenyin
W
Chen
Youcheng
Y
Yuan
Xinrui
X
Zhang
Jin
J
Li
Minghua
M
Tong
Guangze
G
Liu
Song
S
You
Xiangping
X
Kong
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D056487:Chemical and Drug Induced Liver Injury, Chronic / Q000473:pathology / Q000517:prevention & control / Q000628:therapy*; D003579:Cytochrome Reductases / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D008115:Liver Regeneration / Q000235:genetics*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000473:pathology; D028361:Mitochondrial Diseases / Q000139:chemically induced / Q000473:pathology / Q000628:therapy; D050862:Oxidoreductases Acting on Sulfur Group Donors; D051381:Rats; D017207:Rats, Sprague-Dawley
D002251:Carbon Tetrachloride; D003579:Cytochrome Reductases; C500897:GFER protein, human; D050862:Oxidoreductases Acting on Sulfur Group Donors