In vitro and in vivo association of transforming growth factor-beta 1 with hepatic fibrosis.
Despite extensive efforts, little progress has been made in identifying the factors that induce hepatic fibrosis. Transforming growth factor-beta (TGF-beta) has been shown to enhance collagen production, therefore its role in hepatic fibrosis was investigated. Treatment of cultured hepatic cells with TGF-beta 1 increased type I procollagen mRNA levels 13-fold due to post-transcriptional gene regulation. When two animal models of hepatic fibrosis, murine schistosomiasis and CCl4-treated rats, were examined, they both exhibited increased levels of TGF-beta 1 gene expression at times that somewhat preceded the increase in collagen synthesis. In contrast, in murine schistosomiasis, mRNA levels of tumor necrosis factor and interleukin-1 peaked early in the fibrogenic process. Immunohistochemical analysis showed TGF-beta 1 to be present in normal mouse liver and to be markedly increased in mice infected with schistosomiasis. TGF-beta 1 appeared in the hepatic parenchyma, primarily in hepatocytes. These findings strongly suggest a role for TGF-beta 1 in a pathophysiological state.
Czaja
M J
MJ
Albert Einstein College of Medicine, Marion Bessin Liver Research Center, Bronx, New York 10461.
Weiner
F R
FR
Flanders
K C
KC
Giambrone
M A
MA
Wind
R
R
Biempica
L
L
Zern
M A
MA
D000818:Animals; D015152:Blotting, Northern; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism*; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000235:genetics; D008099:Liver / Q000378:metabolism / Q000502:physiology; D008106:Liver Cirrhosis, Experimental / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D051381:Rats; D012555:Schistosomiasis mansoni / Q000378:metabolism*; D014158:Transcription, Genetic; D015291:Transforming Growth Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D015291:Transforming Growth Factors; D003094:Collagen