Transforming growth factor-beta (TGF-beta) isoforms in rat liver regeneration: messenger RNA expression and activation of latent TGF-beta.

Abstract

Expression of transforming growth factor-beta s (TGF-beta s) 1-3 was studied in normal liver and during liver regeneration after partial hepatectomy in the rat to determine whether each of these isoforms might be involved in hepatocyte growth in vivo. Expression of the mRNAs for all three TGF-beta isoforms increases in the regenerating liver. In addition, the levels of expression of the mRNAs for several extracellular matrix proteins, including fibronectin, vitronectin, laminin, and collagen, also increase in the regenerating liver. Immunohistochemical staining analysis shows a similar distribution of all three TGF-beta s in normal and regenerating liver; however, in both tissues, the level of expression of TGF-beta 1 is 8- to 10-fold higher than that of TGF-beta 2 as determined by sandwich enzyme-linked immunosorbent assay. Expression of all three TGF-beta mRNAs is restricted to liver nonparenchymal cells. Although hepatocytes from normal and regenerating livers do not synthesize TGF-beta, they are sensitive to inhibition of growth by all three TGF-beta isoforms. Hepatocytes from regenerating livers are capable of activating latent TGF-beta 1 complexes in vitro, whereas normal hepatocytes are not. The different TGF-beta isoforms may function in an inhibitory paracrine mechanism that is activated during liver regeneration and may also regulate the synthesis of extracellular matrix components in the regenerating liver.

Levels of transforming growth factor β and transforming growth factor β receptors in rat liver during growth, regression by apoptosis and neoplasia

“…Likewise, similar discrepancies have also been observed in cultured mammalian cells and in livers after partial hepatectomy. [10][11][12][13] Explanations for these discrepancies include that extensive post-transcriptional regulation may control the actual protein amount; e.g., retinoic acid prolongs the stability of the TGF-β 1 mRNA, whereas the anti-estrogen tamoxifen has been reported to reduce the translatability of the message. 11,12 There is strong evidence that the 5Ј-UTR region of the TGF-β 1 mRNA regulates expression of the protein by translational mechanisms in a cell-type specific manner.…”

“…10 TGF-β 1 and TβRs I to III in CCl 4 -Intoxicated Liver. A necrogenic dose of CCl 4 was applied which caused the excessive release of intracellular glutamate dehydrogenase to the serum, indicating predominantly lytic forms of cell death (Fig.…”

“…The expression of TGF-β appears to be regulated partially at the post-transcriptional level, which emphasizes the importance of studying the message and the protein of this cytokine. [10][11][12][13][14] The function of this cytokine is dependent on the interaction with surface receptor types I, II, and III (TβRs I-III). TβR III is proposed to be involved in regulating the access of ligand to TβRs I and II.…”

“…In rat liver, TGF-β 1 is the most abundant and important one of the three isoforms, being synthesized predominantly by Ito cells. 3,10,28 Unlike original concepts, evidence suggests that not only mesenchymal cells but also hepatoctyes are able to produce and secrete latent and/or mature TGF-β 1 . 29,30 In livers during and after CPA treatment, we found that hepatocytes which were preparing for apoptosis showed positive immunostaining for the TGF-β 1 precursor protein.…”

Urinary transforming growth factor ?1 levels in hepatitis C virus-related chronic liver disease: Correlation between high levels and severity of disease

“…(HEPAsis. 28,29 Based on the necroinflammatory nature of chronic TOLOGY 1997;25:1141-1146.) viral liver disease, the elevated TGF-b 1 levels might reflect a stimulation of a broad spectrum of cytokines and might not Chronic hepatitis and cirrhosis are late sequelae of chronic be causally related to fibrosis.…”