Differential expression of transforming growth factor-β and its receptors in hepatocytes and nonparenchymal cells of rat liver after CCl4 administration

Up-regulated Transcriptional Repressors SnoN and Ski Bind Smad Proteins to Antagonize Transforming Growth Factor-β Signals during Liver Regeneration

“…This frequently occurs in cancer cells, but it has been also observed in proliferating hepatocytes during liver regeneration (27,60). Several groups have described a downregulation of the TGF-␤ receptors during liver regeneration (25,35,50,61). This process occurs between 24 and 48 h after partial hepatectomy or CCl 4 injury, and it has been associated with the cell insensitivity to TGF-␤ during this period of time.…”

“…All three TGF-␤ isoforms and activin A are up-regulated during the regenerative response to partial hepatectomy (8 -10). Interestingly, during liver regeneration, hepatocytes become refractory to TGF-␤ signals, and the liver can still growth despite the presence of this cytokine, although the mechanisms involved are not known (25,60). Liver regeneration after partial hepatectomy is an extensively studied model of hepatocyte proliferation (11)(12)(13).…”

“…During liver regeneration, there is an increase in TGF-␤ mRNA and protein levels, but it is not known whether the TGF-␤ is active or latent (8). In addition, hepatocytes become refractory to TGF-␤ signals during liver regeneration (25,60). In this study, we set about to investigate the activation state of the TGF-␤/Smad pathway during liver regeneration and to explore the mechanisms of hepatocyte resistance to TGF-␤ during this process.…”

Distortion of autocrine transforming growth factor β signal accelerates malignant potential by enhancing cell growth as well as PAI-1 and VEGF production in human hepatocellular carcinoma cells

“…Northern blot hybridization analysis mRNAs were isolated and hybridized with labeled cDNA probes for TGF-b 1 , Smad2, Smad3, PAI-1, and human GAPDH as described (Date et al, 1998). To determine human VEGF mRNA levels, 0.52-kb PCR (forward, 5 0 -GACG-CCCTCCGAAACCATGAAC-3 0 ; reverse, 5 0 -CAGCCTG-GCTCACCGCCTTG-3 0 ) fragment of mouse VEGF was used as the cDNA probe.…”

Synaptophysin: A Novel Marker for Human and Rat Hepatic Stellate Cells

“…Hepatic stellate cells have been demonstrated to be involved in conditions ranging from acute necrotizing and regenerating liver disorders [1][2][3] to chronic and fibrosing hepatic diseases. 4 -6 Essential functions exerted in these conditions are the production of extracellular matrix components, 7-9 the production of transforming growth factor ␤1 (TGF-␤1) 10,11 and hepatocyte growth factor (HGF), [12][13][14][15][16] and the role of effector cell responsible for microvascular tone regulation in the liver. 17,18 Based on their expression of vimentin, desmin, and ␣-smooth muscle actin (␣-SMA), 19 -24 stellate cells have been considered to be of mesenchymal origin.…”