scholarly journals Activation of Ito cells involves regulation of AP-1 binding proteins and induction of type I collagen gene expression

1994 ◽  
Vol 304 (3) ◽  
pp. 817-824 ◽  
Author(s):  
J Armendariz-Borunda ◽  
C P Simkevich ◽  
N Roy ◽  
R Raghow ◽  
A H Kang ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Binding Proteins ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Collagen Type I ◽  
Type I ◽  
Tgf Beta ◽  
Ito Cells ◽  
Nuclear Extracts ◽  
I Gene

Activation of liver Ito cells is characterized by increased proliferation, fibrogenesis, loss of cellular retinoid and change of cell-shape. Here, we have described fundamental differences between freshly isolated Ito cells (FIC) and long-term cultured Ito cells (LTIC). This process of activation correlates with the absence of expression of Pro alpha 1(I) gene in FIC. LTIC expressed abundant transcripts of Pro alpha 1(I) gene. Nuclear run-off experiments showed the inability of FIC to support Pro alpha 1(I) RNA transcription while LTIC transcribed it greater than 5-fold as compared with FIC. Transforming growth factor beta (TGF beta)-treated LTIC had a preferential increase in the rate of Pro alpha 1(I) gene transcription as compared with control LTIC. A human collagen type I promoter-enhancer construct (pCOL-KT) [Thompson, Simkevich, Holness, Kang and Raghow (1991) J. Biol. Chem. 266, 2549-2556] was readily expressed in LTIC but failed to be expressed in FIC. Furthermore, TGF beta treatment of LTIC resulted in an increased expression of pCOL-KT. The deletion of an activator protein-1 (AP-1) binding site (+598 to +604) in the 360 bp enhancer region of pCOL-KT (S360) caused decreased expression of the CAT reporter gene, suggesting that this bonafide AP-1 site can, at least in part, mediate the transactivation effect of TGF beta. Using DNAase I protection, we demonstrate a single foot-print located at +590 to +625 in the S360 fragment; nuclear extracts prepared from TGF beta-treated LTIC exhibited greater activity of these AP-1 binding proteins. Gel mobility assays corroborated and extended the footprinting observation. No AP-1-binding activity was found in the nuclear extracts of FIC. Double-stranded oligonucleotides containing the consensus AP-1 motif were able to compete out the binding; consensus NF-1 motif oligonucleotides failed to do so. The preincubation of nuclear extracts from control and TGF beta-treated LTIC with antibodies against c-jun and c-fos rendered a reduced binding of AP-1 proteins to the target S360 fragment.

scholarly journals Transforming-growth-factor-β activation elements in the distal promoter regions of the rat α1 type I collagen gene

1991 ◽  
Vol 280 (1) ◽  
pp. 157-162 ◽  
Author(s):  
J D Ritzenthaler ◽  
R H Goldstein ◽  
A Fine ◽  
A Lichtler ◽  
D W Rowe ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transcriptional Activation ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Collagen Type I ◽  
Type I ◽  
Tgf Beta ◽  
Mobility Shift

We have located a cis-acting element (alpha 1-TAE) within the promoter sequences of the rat collagen alpha 1(I) gene (COL1A1) 1600 bases upstream of the transcription start site which mediates transcriptional activation by transforming growth factor beta (TGF-beta). The functional significance of this region was established by (1) deletion analysis of the alpha 1(I) promoter cloned upstream of the bacterial chloramphenicol acetyltransferase (CAT) gene and (2) by co-transfection of promoter constructs with double-stranded oligonucleotides. DNA-mobility-shift assays with radiolabelled alpha 1-TAE demonstrated increased nuclear binding activity after TGF-beta stimulation. Oligonucleotides encoding the alpha 1-TAE, additional upstream regions within the alpha 1(I) promoter, as well as consensus nuclear-factor-1 (NF-1) sequences, competed with the alpha 1-TAE sequence. The two collagen type I genes are stimulated by TGF-beta through different regions of their promoters.

Altered expression of type I collagen, TGF-beta 1, and related genes in rat lung exposed to 85% O2

1995 ◽  
Vol 268 (1) ◽  
pp. L78-L84 ◽  
Author(s):  
A. M. Moore ◽  
S. Buch ◽  
R. N. Han ◽  
B. A. Freeman ◽  
M. Post ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Type I ◽  
Tgf Beta ◽  
Pulmonary Epithelium ◽  
Gene Expressions ◽  
Altered Expression ◽  
Growth Factor Beta ◽  
Interstitial Collagenase

The gene expressions of type I collagen and transforming growth factor-beta 1 (TGF-beta 1) were studied in lung tissue of rats exposed to air or 85% O2 for 14 days. Peak expression of type I collagen mRNA was observed by 14 days of 85% O2 exposure, at the same time as maximal immunoreactive type I collagen, which was most marked surrounding the major airways and vessels. TGF-beta 1 mRNA also significantly increased after 14, but not 4 or 6 days of 85% O2 exposure. TGF-beta 1 immunoreactivity was only detected on day 14 of 85% O2 exposure and was localized primarily to the pulmonary epithelium. As an increase in immunoreactive type I collagen was evident by day 6 of O2 exposure, the gene expressions of interstitial collagenase (MMP-1), stromelysin, and the tissue inhibitor of the metalloproteinases (TIMP) were also examined. Increased mRNA expressions of interstitial collagenase and TIMP preceded those of type I collagen and TGF-beta 1, occurring at 4-6 days of exposure to 85% O2, while there was no significant change in stromelysin mRNA. These findings are compatible with the initial O2-mediated increase in type I collagen deposition being a result of an altered proteinase/antiproteinase balance in the lung, and the subsequent more marked deposition being a response to increased TGF-beta 1 synthesis.

Cloning of a growth arrest-specific and transforming growth factor beta-regulated gene, TI 1, from an epithelial cell line

1991 ◽  
Vol 11 (10) ◽  
pp. 5338-5345
Author(s):  
B Kallin ◽  
R de Martin ◽  
T Etzold ◽  
V Sorrentino ◽  
L Philipson
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Lung Epithelial Cells ◽  
Epithelial Cell Line ◽  
Type I ◽  
Tgf Beta ◽  
Protein Synthesis Inhibitors ◽  
Plasminogen Activator Inhibitor 1 ◽  
Growth Factor Beta

By cDNA cloning and differential screening, five genes that are regulated by transforming growth factor beta (TGF beta) in mink lung epithelial cells were identified. A novel membrane protein gene, TI 1, was identified which was downregulated by TGF beta and serum in quiescent cells. In actively growing cells, the TI 1 gene is rapidly and transiently induced by TGF beta, and it is overexpressed in the presence of protein synthesis inhibitors. It appears to be related to a family of transmembrane glycoproteins that are expressed on lymphocytes and tumor cells. The four other genes were all induced by TGF beta and correspond to the genes of collagen alpha type I, fibronectin, plasminogen activator inhibitor 1, and the monocyte chemotactic cell-activating factor (JE gene) previously shown to be TGF beta regulated.

scholarly journals Stimulation of the chemotactic migration of human fibroblasts by transforming growth factor beta.

1987 ◽  
Vol 165 (1) ◽  
pp. 251-256 ◽  
Author(s):  
A E Postlethwaite ◽  
J Keski-Oja ◽  
H L Moses ◽  
A H Kang
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Human Fibroblasts ◽  
Critical Role ◽  
Dermal Fibroblasts ◽  
Type I ◽  
Tgf Beta ◽  
Chemotactic Migration ◽  
Growth Factor Beta

Transforming growth factor beta (TGF-beta) is a potent chemoattractant in vitro for human dermal fibroblasts. Intact disulfide and perhaps the dimeric structure of TGF-beta is essential for its ability to stimulate chemotactic migration of fibroblasts, since reduction with 2-ME results in a marked loss of its potency as a chemoattractant. Although epidermal growth factor (EGF) appears to be capable of modulating some effects of TGF-beta, it does not alter the chemotactic response of fibroblasts to TGF-beta. Specific polyvalent rabbit antibodies to homogeneously pure TGF-beta block its chemotactic activity but has no effect on the other chemoattractants tested (platelet-derived growth factor, fibronectin, and denatured type I collagen). Since TGF-beta is secreted by a variety of neoplastic and normal cells including platelets, monocytes/macrophages, and lymphocytes, it may play a critical role in vivo in embryogenesis, host response to tumors, and the repair response that follows damage to tissues by immune and nonimmune reactions.

TGF-beta and collagen-alpha 1 (I) gene expression are increased in hepatic acinar zone 1 of rats with iron overload

1994 ◽  
Vol 267 (5) ◽  
pp. G908-G913 ◽  
Author(s):  
K. Houglum ◽  
P. Bedossa ◽  
M. Chojkier
Keyword(s):  
Gene Expression ◽  
Lipid Peroxidation ◽  
Iron Overload ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Cultured Cells ◽  
Collagen Gene ◽  
Tgf Beta ◽  
Collagen Gene Expression ◽  
I Gene

We have shown that lipid peroxidation stimulates collagen-alpha 1 (I) gene transcription in cultured cells. Because iron is a transitional metal known to induce lipid peroxidation, we investigated whether hepatic lipid peroxidation modulates collagen gene expression in iron-overloaded rats. In this animal model of hemochromatosis, we show colocalization with iron in the hepatic acinar zone 1 of both lipid peroxidation and increased collagen-alpha 1 (I) transcripts, using immunohistochemistry for malondialdehyde-protein adducts and in situ hybridization, respectively. Iron overload stimulated the expression of the cytokine transforming growth factor-beta (TGF-beta) in acinar zone 1, in spite of the minor degree of hepatocellular necrosis and inflammation. The formation of reactive aldehydes and TGF-beta, both inducers of collagen gene expression, may play a role in the stimulation of hepatic collagen production in iron overload. These mechanisms could be a link between iron overload and fibrosis in genetic hemochromatosis.

scholarly journals Retinoic acid and transforming growth factor β differentially inhibit platelet-derived-growth-factor-induced Ito-cell activation

1991 ◽  
Vol 278 (1) ◽  
pp. 43-47 ◽  
Author(s):  
B H Davis ◽  
U R Rapp ◽  
N O Davidson
Keyword(s):  
Retinoic Acid ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Cell Activation ◽  
Cellular Proliferation ◽  
Transforming Growth Factor ◽  
Platelet Derived Growth Factor ◽  
Tgf Beta ◽  
Ito Cell ◽  
Ito Cells

Sinusoidal Ito cells (stellate or fat-storing cells) undergo excessive cellular proliferation before the establishment and progression of hepatic fibrosis and cirrhosis. Retinoic acid and transforming growth factor beta (TGF beta) both inhibit Ito-cell [3H]thymidine incorporation in serum-containing media. Serum-induced mitogenicity was dependent on platelet-derived growth factor (PDGF). Additionally, pre-treatment of Ito cells with retinoic acid and TGF beta blocked PDGF-induced cell proliferation. TGF beta, but not retinoic acid, diminished PDGF-receptor and smooth-muscle alpha-actin abundance.

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