scholarly journals TGF beta inhibits HGF, FGF7, and FGF10 expression in normal and IPF lung fibroblasts

2018 ◽  
Vol 6 (16) ◽  
pp. e13794 ◽  
Author(s):  
Kelly A. Correll ◽  
Karen E. Edeen ◽  
Elizabeth F. Redente ◽  
Rachel L. Zemans ◽  
Benjamin L. Edelman ◽  
...  
Keyword(s):  
Lung Fibroblasts ◽  
Tgf Beta ◽  
Fgf10 Expression

Latent TGF-beta binding protein LTBP-1 contains three potential extracellular matrix interacting domains

2001 ◽  
Vol 114 (1) ◽  
pp. 187-197 ◽  
Author(s):  
C. Unsold ◽  
M. Hyytiainen ◽  
L. Bruckner-Tuderman ◽  
J. Keski-Oja
Keyword(s):  
Extracellular Matrix ◽  
Expression System ◽  
Covalent Binding ◽  
Sodium Deoxycholate ◽  
Current Data ◽  
Lung Fibroblasts ◽  
Tgf Beta ◽  
Mammalian Expression ◽  
The Matrix ◽  
Recombinant Fragments

Latent TGF-beta binding proteins (LTBPs) are components of the extracellular matrix (ECM). They belong to the fibrillin/LTBP-superfamily, and are high molecular weight glycoproteins characterized by EGF-like repeats and 8-Cys repeats. Most LTBPs associate with the small latent forms of TGF-beta. Their roles include to facilitate the secretion of latent TGF-beta and to target it to the ECM. In order to identify new matrix-binding domains of LTBP-1 and to characterize their association with the extracellular matrix, we have produced (in a mammalian expression system) partly overlapping recombinant fragments of its shorter form, LTBP-1S, and analyzed the binding of the purified fusion proteins to extracellular matrices of cultured human dermal and lung fibroblasts. Recombinant fragments from three different regions of the N- and C-termini showed affinity to the matrix. These interacting regions contain either the first (hybrid), second or fourth 8-Cys domains of the LTBP-1S molecule. They bound independently to the matrix. Each of them had an ability to inhibit the association of native exogenous LTBP-1 with fibroblast extracellular matrix. The interactions of the LTBP-1 fragments with the extracellular matrix resisted treatment with sodium deoxycholate, suggesting strong, possibly covalent binding. The binding occurred in a time- and dose-dependent fashion. The N-terminal fragments bound more readily to the matrices. With all fragments the binding took place both with intact fibroblast matrices and with matrices isolated by sodium deoxycholate. When using CHO cell layers, which form sparse matrices, only the N-terminal fragment of LTBP-1 was efficiently incorporated. The association of the binding fragments with isolated matrices was enhanced by soluble, cell-derived factors. The current data suggest that LTBP-1 contains three different domains with an ability to associate with the extracellular matrix.

scholarly journals Regulation of fibroblast procollagen production. Transforming growth factor-β1 induces prostaglandin E2 but not procollagen synthesis via a pertussis toxin-sensitive G-protein

1995 ◽  
Vol 307 (1) ◽  
pp. 63-68 ◽  
Author(s):  
R J McAnulty ◽  
R C Chambers ◽  
G J Laurent
Keyword(s):  
Growth Factor ◽  
Prostaglandin E2 ◽  
G Protein ◽  
Pertussis Toxin ◽  
Transforming Growth Factor ◽  
Pge2 Production ◽  
Lung Fibroblasts ◽  
Extracellular Matrix Protein ◽  
Dependent Manner ◽  
Tgf Beta

Transforming growth factor-beta 1 (TGF beta 1) initiates a series of signalling events resulting in diverse cellular responses including stimulation of extracellular matrix protein production. In this study we have investigated the role of pertussis toxin-sensitive G-proteins in mediating the effects of TGF beta 1 on fibroblast procollagen metabolism. TGF beta 1 stimulated human fetal lung fibroblast procollagen synthesis and production in a dose-dependent manner which was maximal at 0.5 ng/ml. TGF beta 1 also decreased the proportion of newly synthesized procollagen degraded intracellularly. Pertussis toxin, a G-protein inhibitor, further stimulated TGF beta 1-induced procollagen synthesis and production, but alone it had no effect on fibroblast procollagen metabolism. Addition of indomethacin also potentiated the TGF beta 1-induced increase in procollagen synthesis and production. The effects of pertussis toxin and indomethacin were not additive. Pertussis toxin and indomethacin did not affect the proportion of newly synthesized procollagen degraded intracellularly, either alone or in combination, by control cells. The TGF beta 1-induced decrease in intracellular procollagen degradation was maintained but not further affected by pertussis toxin or indomethacin. TGF beta 1 increased prostaglandin E2 (PGE2) compared with PGE2 production by control cells. Addition of pertussis toxin or indomethacin blocked the TGF beta 1-induced increase in PGE2 production. The TGF beta 1-induced increase in PGE2 preceded the increase in procollagen production. These results demonstrate that TGF beta 1-induced procollagen synthesis by lung fibroblasts is modulated by production of PGE2. Pertussis toxin and indomethacin block the production of PGE2 and enhance the effect of TGF beta 1 on procollagen synthesis. From these data we conclude that the effects of TGF beta 1 on PGE2 production but not procollagen synthesis are mediated via a receptor linked to a pertussis toxin-sensitive G-protein.

Cytokine signaling in lung: transforming growth factor-beta secretion by lung fibroblasts

1991 ◽  
Vol 260 (2) ◽  
pp. L123-L128 ◽  
Author(s):  
J. Kelley ◽  
J. P. Fabisiak ◽  
K. Hawes ◽  
M. Absher
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Phenotypic Expression ◽  
Soft Agar ◽  
Lung Fibroblast ◽  
Lung Fibroblasts ◽  
Tgf Beta ◽  
Anchorage Independent Growth ◽  
Growth Factor Beta

Control of growth and phenotypic expression of interstitial fibroblasts is a critical determinant of lung architecture and physiology during processes of growth and remodeling. We examined the ability of lung fibroblasts to produce transforming growth factor-beta (TGF-beta), a cytokine that is known to modulate proliferation and phenotypic expression of mesenchymal cells. Cultures of fibroblasts isolated from rat lungs spontaneously secrete TGF-beta as measured in the standard bioassay of anchorage-independent growth of normal rat kidney (NRK) cells in soft agar. Rat lung fibroblasts secrete TGF-beta in an inactive precursor form. Fibroblasts cultured from adult and fetal rat lungs produced comparable amounts of TGF-beta. The ability of lung fibroblast supernatant fluids to induce colony formation in soft agar could be completely neutralized by preincubation of samples with anti-TGF-beta immunoglobulin (Ig). Anti-platelet-derived growth factor IgG had no effect on anchorage-independent growth of NRK cells driven by rat fibroblast culture supernatant samples. These results indicate that TGF-beta does not require the presence of and interaction with secondary cytokines for its activity. In contrast to the results obtained with rat cells, neither human fetal nor adult lung fibroblasts secreted detectable amount of active TGF-beta or its inactive precursor. This was not due to the presence of TGF-beta inhibitors in fibroblast culture media, because the addition of purified porcine TGF-beta to conditioned medium from human lung fibroblast cultures yielded the expected increase in NRK cell growth in soft agar. These results point to differing cytokine control patterns in the lungs of the two species.

scholarly journals Enhanced production and extracellular deposition of the endothelial-type plasminogen activator inhibitor in cultured human lung fibroblasts by transforming growth factor-beta.

1986 ◽  
Vol 103 (6) ◽  
pp. 2403-2410 ◽  
Author(s):  
M Laiho ◽  
O Saksela ◽  
P A Andreasen ◽  
J Keski-Oja
Keyword(s):  
Growth Factor ◽  
Plasminogen Activator ◽  
Transforming Growth Factor Beta ◽  
Culture Medium ◽  
Transforming Growth Factor ◽  
Lung Fibroblasts ◽  
Tissue Type ◽  
Metabolic Labeling ◽  
Tgf Beta ◽  
Growth Factor Beta

Cultured human embryonic lung fibroblasts were used as a model to study the effects of transforming growth factor-beta (TGF beta) on the plasminogen activator (PA) activity released by nontumorigenic cells into the culture medium. The cells were exposed to TGF beta under serum-free conditions, and the changes in PA activity and protein metabolism were analyzed by caseinolysis-in-agar assays, zymography, and polypeptide analysis. Treatment of the cells with TGF beta caused a significant decrease in the PA activity of the culture medium as analyzed by the caseinolysis-in-agar assays. The quantitatively most prominent effect of TGF beta on confluent cultures of cells was the induction of an Mr 47,000 protein, as detected by metabolic labeling. The Mr 47,000 protein was a PA inhibitor as judged by reverse zymography. It was antigenically related to a PA inhibitor secreted by HT-1080 tumor cells as demonstrated with monoclonal antibodies. The induced Mr 47,000 inhibitor was deposited into the growth substratum of the cells, as detected by metabolic labeling, immunoblotting analysis, and reverse zymography assays of extracellular matrix preparations. TGF beta also decreased the amounts of urokinase-type and tissue-type PAs accumulated in the conditioned medium, as detected by zymography. Epidermal growth factor antagonized the inhibitory effects of TGF beta by enhancing the amounts of the PAs. These results indicate that growth factors modulate the proteolytic balance of cultured cells by altering the amounts of PAs and their inhibitors.

scholarly journals Effect of transforming growth factor-β1 and basic fibroblast growth factor on the expression of cell surface proteoglycans in human lung fibroblasts. Enhanced glycanation and fibronectin-binding of CD44 proteoglycan, and down-regulation of glypican

1995 ◽  
Vol 310 (1) ◽  
pp. 73-81 ◽  
Author(s):  
M Romarís ◽  
A Bassols ◽  
G David
Keyword(s):  
Growth Factor ◽  
Cell Surface ◽  
Fibroblast Growth Factor ◽  
Transforming Growth Factor ◽  
Human Lung ◽  
Core Protein ◽  
Lung Fibroblasts ◽  
Fibroblast Growth ◽  
Tgf Beta ◽  
Human Lung Fibroblasts

We have tested the effects of transforming growth factor-beta 1 (TGF-beta 1), basic fibroblast growth factor (bFGF) and TGF-beta 1 + bFGF on the expression of the cell surface proteoglycans (CD44, syndecans and glypican) in cultures of human lung fibroblasts (HLF). Cell surface proteoglycan expression was monitored by quantitative immunoprecipitation from metabolically labelled cells. Western and Northern blotting and evaluation of the glycanation of the proteoglycans. Stimulation of the cells with TGF-beta 1 increased the length of the chondroitin sulphate (CS) chains on CD44 (approximately 1.6-fold). bFGF, administered solely, also increased the length of the CS chains on CD44 (approximately 1.4-fold), whereas the combination of TGF-beta 1 + bFGF nearly doubled both the length and the number of the CS chains on CD44. None of these treatments lead to changes in CD44 message or core-protein expression. This enhanced glycanation of CD44 after the TGF-beta 1, bFGF and combined treatments correlated with a 2-fold increase in the affinity of the proteoglycan for fibronectin but had no influence on the binding to type I collagen. TGF-beta 1, alone or in combination with bFGF, also stimulated the CS content of syndecan-1, but none of the other syndecans was significantly affected by any of the factors or combinations tested. The expression of glypican however was significantly decreased (nearly halved) by the combination of TGF-beta 1 + bFGF, less so by TGF-beta 1 and not at all by bFGF. This decrease occurred both at the level of the message and of the core protein. These data demonstrate specific and differential effects of TGF-beta 1 and bFGF on the structure, expression and interactions of the cell surface proteoglycans of HLF.

Influences of endogenous and exogenous TGF-beta on elastin in rat lung fibroblasts and aortic smooth muscle cells

1992 ◽  
Vol 263 (2) ◽  
pp. L257-L263 ◽  
Author(s):  
S. E. McGowan
Keyword(s):  
Smooth Muscle ◽  
Steady State ◽  
Smooth Muscle Cells ◽  
Culture Medium ◽  
Muscle Cells ◽  
Neonatal Rat ◽  
Lung Fibroblasts ◽  
Rat Lung ◽  
Tgf Beta ◽  
Adult Rats

The factors that regulate elastin production during neonatal lung development have not been elucidated. Previous investigations suggested that transforming growth factor-beta (TGF-beta) increases elastin production by neonatal rat lung fibroblasts (LF). We examined whether this effect of TGF-beta was unique to these cells or was evident in other neonatal cells, which constitutively produce elastin, or in cells from adults, whose constitutive elastin production is low. We have quantitated soluble elastin, elastin mRNA, and TGF-beta production in primary cultures of smooth muscle cells (SMC) and LF from neonatal and adult rats and have examined the alterations in soluble elastin and elastin mRNA that result from adding 100 pM exogenous TGF-beta 1 to these cultures. Unsupplemented cultures of LF and SMC obtained from neonatal rats exhibited higher steady-state levels of elastin mRNA and contained more soluble elastin in their culture medium than did cells from adult animals. When neonatal LF were supplemented with 100 pM TGF-beta 1, they showed a significant increase in the soluble elastin content of their culture medium and their steady-state elastin mRNA. Neither LF obtained from adults nor SMC obtained from neonatal or adult rats significantly increased their soluble elastin or steady-state elastin mRNA after the addition of exogenous TGF-beta. When neonatal LF were supplemented with an anti-TGF-beta neutralizing antibody, the soluble elastin content of the culture medium decreased significantly. These data suggest that the responsiveness of elastin expression to TGF-beta is limited to neonatal LF and that endogenous TGF-beta influences elastin production by neonatal LF.

Modulation of bFGF in lung fibroblasts by TGF-beta and PDGF

1991 ◽  
Vol 261 (6) ◽  
pp. L378-L385 ◽  
Author(s):  
K. T. Goldsmith ◽  
R. B. Gammon ◽  
R. I. Garver
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Calf Serum ◽  
Fold Increase ◽  
Fibroblast Cell ◽  
Lung Fibroblasts ◽  
Tgf Beta ◽  
Human Lung Fibroblast

Growth factors produced by alveolar macrophages are thought to promote the fibroblast proliferation within interstitial spaces of fibrotic lungs. This study investigated the possibility that the macrophage-produced growth factors might modulate the expression of basic fibroblast growth factor (bFGF) by lung fibroblasts. To evaluate this question, bFGF gene expression and protein production were evaluated in normal adult human lung fibroblast cell lines. Under normal culture conditions, the fibroblasts expressed the bFGF gene as two major transcripts (7.1, 3.7 kb). The addition of fetal calf serum (FCS) to serum-starved fibroblasts caused a 5- to 10-fold increase in bFGF expression. Steady-state bFGF expression was increased 108% by platelet-derived growth factor (PDGF) and 602% by transforming growth factor-beta (TGF-beta). Insulin-like growth factor-1 had no significant effect on bFGF expression. Nuclear runoff studies demonstrated that both PDGF and TGF-beta increased the relative rates of bFGF transcription in the fibroblasts. Western blot analysis of lysates from fibroblasts treated with either PDGF or TGF-beta had no detectable increase in bFGF protein above unstimulated controls. However, the simultaneous addition of PDGF and TGF-beta, or FCS, produced a marked increase in bFGF. These experiments show that two growth factors present in the alveolar airspace compartment of fibrotic lungs can promote the expression of bFGF within lung fibroblasts.

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