Blockade of type beta transforming growth factor signaling prevents liver fibrosis and dysfunction in the rat.

Abstract	We eliminated type beta transforming growth factor (TGF-beta) signaling by adenovirus-mediated local expression of a dominant-negative type II TGF-beta receptor (AdCATbeta-TR) in the liver of rats treated with dimethylnitrosamine, a model of persistent liver fibrosis. In rats that received a single application of AdCATbeta-TR via the portal vein, liver fibrosis as assessed by histology and hydroxyproline content was markedly attenuated. All AdCATbeta-TR-treated rats remained alive, and their serum levels of hyaluronic acid and transaminases remained at low levels, whereas all the AdCATbeta-TR-untreated rats died of liver dysfunction. The results demonstrate that TGF-beta does play a central role in liver fibrogenesis and indicate clearly in a persistent fibrosis model that prevention of fibrosis by anti-TGF-beta intervention could be therapeutically useful.
Authors	Z Qi, N Atsuchi, A Ooshima, A Takeshita, H Ueno
Journal	Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 96 Issue 5 Pg. 2345-9 (Mar 02 1999) ISSN: 0027-8424 [Print] United States
PMID	10051644 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Receptors, Transforming Growth Factor beta Recombinant Fusion Proteins Transforming Growth Factor beta Hyaluronic Acid Aspartate Aminotransferases Alanine Transaminase Protein Serine-Threonine Kinases Receptor, Transforming Growth Factor-beta Type II Dimethylnitrosamine
Topics	Adenoviridae Alanine Transaminase (blood) Animals Aspartate Aminotransferases (blood) Body Weight Dimethylnitrosamine Genetic Therapy (methods) Genetic Vectors Hyaluronic Acid (blood) Liver (drug effects, pathology) Liver Cirrhosis, Experimental (pathology, physiopathology, prevention & control) Male Protein Serine-Threonine Kinases Rats Rats, Sprague-Dawley Receptor, Transforming Growth Factor-beta Type II Receptors, Transforming Growth Factor beta (genetics, physiology) Recombinant Fusion Proteins (biosynthesis) Signal Transduction Survival Rate Transforming Growth Factor beta (antagonists & inhibitors, physiology)

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