scholarly journals Association of fibroblast growth factor 10 with the fibrotic and inflammatory pathogenesis of Graves’ orbitopathy

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255344
Author(s):  
Sun Young Jang ◽  
Soo Hyun Choi ◽  
Don Kikkawa ◽  
Eun Jig Lee ◽  
Jin Sook Yoon
Keyword(s):  
Growth Factor ◽  
Protein Expression ◽  
Fibroblast Growth Factor ◽  
Transforming Growth Factor ◽  
Fibroblast Growth ◽  
Expression Levels ◽  
Tnf Α ◽  
Orbital Tissue ◽  
Graves Orbitopathy ◽  
Tgf Β1

Purpose The role of fibroblast growth factor (FGF) in orbital fibroblasts (OFs) is rarely known. In this study, we investigated the effect of FGF10 on fibrosis and the inflammation mechanism of Graves′ orbitopathy (GO). Methods Orbital tissue from GO (n = 15) and non-GO (n = 15) was obtained for this study. The mRNA and protein expression levels of FGF10 and FGF receptor 2b (FGFR2b) in orbital tissue were determined by real-time polymerase chain reaction, western blot analysis, and confocal microscopy. The effects of FGF10 on transforming growth factor (TGF)-β1 induced fibrotic proteins and interleukin (IL)-1β- or tumor necrosis factor (TNF)-α- induced inflammatory proteins were investigated using recombinant human (rh) FGF10 and small interfering (si) RNA transfection against FGF10. Results FGF10 and FGFR2b mRNA expression levels were significantly lower in GO orbital tissues than in non-GO orbital tissues (p = 0.009 and 0.005, respectively). Immunostaining of FGF10 in orbital adipose tissues showed differences in FGF10 expression between GO and control samples. Immunostaining of FGF10 was very weak in the orbital tissues of GO patients. TGF-β1-induced fibronectin, collagen Iα, α-smooth muscle actin protein expression in GO OFs was attenuated by rhFGF10 treatment and increased by knockdown of FGF10 via siFGF10 transfection. Similarly, IL-1β- or TNF-α-induced IL-6, IL-8, and cyclooxygenase-2 protein production in GO OFs was either blocked by rhFGF10 treatment or further upregulated by inhibition of FGF10 via siFGF10 transfection. Conclusions Our data demonstrate that FGF10 has beneficial effects on the inflammatory and fibrotic mechanisms of GO in primary cultured OFs, providing new insights into GO pathology and the discovery of FGF10 as a promising novel therapeutic application for the treatment of GO.

scholarly journals Latent transforming growth factor-β complex in Chinese hamster ovary cells contains the multifunctional cysteine-rich fibroblast growth factor receptor, also termed E-selectin-ligand or MG-160

1997 ◽  
Vol 324 (2) ◽  
pp. 427-434 ◽  
Author(s):  
Anders OLOFSSON ◽  
Ulf HELLMAN ◽  
Peter TEN DIJKE ◽  
Susanne GRIMSBY ◽  
Hidenori ICHIJO ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Major Part ◽  
Transforming Growth Factor ◽  
Chinese Hamster ◽  
Transforming Growth Factor Β ◽  
Cell Types ◽  
Fibroblast Growth ◽  
Selectin Ligand ◽  
Tgf Β1

Transforming growth factor-β (TGF-β) is secreted as latent high molecular mass complexes from producer cells. The N-terminal precursor remnant, also called latency-associated peptide (LAP), forms a non-covalently linked complex with TGF-β and confers the latency to TGF-β. In human platelets and certain other cell types, latent TGF-β binding protein-1 (LTBP-1) is disulphide-linked to LAP, and forms complexes of more than 230 kDa. In addition, LTBP-2 and -3, which are structurally similar to LTBP-1, can be part of latent TGF-β complexes. In Chinese hamster ovary (CHO) cells transfected with the TGF-β1 cDNA, a major part of the latent TGF-β secreted into the medium is a 100-kDa small latent complex containing TGF-β and LAP. In addition, we found two other forms of latent TGF-β complexes, i.e. a 220-kDa complex containing LTBP-1, and a 220-kDa complex containing a 140-kDa protein. Purification of the 140-kDa component, termed latent TGF-β complexed protein-1 (LTCP-1), followed by amino acid sequencing and cDNA cloning from a CHO cell cDNA library, revealed that it is a hamster counterpart of a previously identified, multifunctional protein known as chicken cysteine-rich fibroblast growth factor (FGF) receptor, mouse E-selectin-ligand and rat MG-160 (a 160-kDa membrane sialoglycoprotein of the Golgi apparatus). Immunoprecipitation of LTCP-1 and TGF-β1 from CHO cells stably transfected with TGF-β1 precursor cDNA revealed that the expressed protein forms a complex with LAP, and that a major part of the complex is secreted. Northern blot analysis showed that mRNA for LTCP-1 was expressed in large amounts in testis, ovary and placenta, but less abundantly in other tissues. These results suggest that TGF-β, produced in certain cell types, may form a complex with LTCP-1, which may have different properties compared with other latent TGF-β complexes. It remains to be investigated whether the complex formation between LTCP-1 and TGF-β1 also occurs in other cells, whether the association between them occurs in the Golgi complex, and whether it affects the interaction of LTCP-1 with FGF or E-selectin.

scholarly journals Fibroblast Growth Factor-1 Suppresses TGF-β-Mediated Myofibroblastic Differentiation of Rat Hepatic Stellate Cells

2016 ◽  
Vol 59 (4) ◽  
pp. 124-132
Author(s):  
Eva Peterová ◽  
Lucie Podmolíková ◽  
Martina Řezáčová ◽  
Alena Mrkvicová
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Hepatic Stellate Cells ◽  
Transforming Growth Factor ◽  
Collagen Gel ◽  
Stellate Cells ◽  
Critical Event ◽  
Fibroblast Growth ◽  
Enhanced Production ◽  
Tgf Β1

Myofibroblast expansion is a critical event in the pathogenesis of liver fibrosis. The activation of hepatic stellate cells (HSC) to myofibroblast (MFB) results in the enhanced production of extracellular matrix (ECM). In this study, we explored the effect of acidic fibroblast growth factor (FGF-1) treatment on a transforming growth factor (TGF-β1) induced MFB conversion. We used HSC-T6 cell line, which represents well-established model of activated HSC. These cells strongly expressed α-smooth muscle actin (α-SMA) and fibronectin (FN-EDA) after stimulation with TGF-β1, which is a stimulus for MFB differentiation and ECM production. FGF-1 reduced proteins expression to levels comparable with untreated cells. Mild repression of secreted gelatinases was seen in culture media after FGF-1 treatment. The exposure of cells to collagen gel leads to changes in cell morphology and in expression of MFB markers. Lack of α-SMA in cells embedded to collagen gel was detected. When stimulated with TGF-β1, the cells increased expression of FN-EDA, but not α-SMA. Although the cells on plastic and in collagen gel show different properties, FGF-1 reduced expression of FN-EDA in both conditions. Disrupting TGF-β1 signalling pathway represents a potential strategy for the treatment of fibrosis. We showed that FGF-1 could antagonize signals initiated by TGF-β1.

TGF-β1 and fibroblast growth factor-1 modify fibroblast growth factor-2 production in type II cells

2000 ◽  
Vol 279 (6) ◽  
pp. L1038-L1046 ◽  
Author(s):  
Cheng-Ming Li ◽  
Jody Khosla ◽  
Ines Pagan ◽  
Paul Hoyle ◽  
Philip L. Sannes
Keyword(s):  
Growth Factor ◽  
Dna Synthesis ◽  
Fibroblast Growth Factor ◽  
Transforming Growth Factor ◽  
Alveolar Epithelium ◽  
Alveolar Type ◽  
Type Ii Cells ◽  
Type Ii ◽  
Fibroblast Growth ◽  
Tgf Β1

Fibroblast growth factor (FGF)-2, which stimulates DNA synthesis by type II cells in the lung, has been shown to be regulated by transforming growth factor (TGF)-β1, an important inflammatory cytokine, in vascular epithelium. The goal of this study was to determine if FGF-2 production by alveolar type II cells is modulated by TGF-β1 or FGF-1, which also stimulates DNA synthesis by type II cells. Isolated rat type II cells were exposed to 0–40 ng/ml of TGF-β1 or 0–500 ng/ml of FGF-1 in serum-free medium for 1–5 days. With a specific immunoassay, significant increases of FGF-2 protein in type II cell lysates to levels above those in control cells were achieved after 1 day of exposure to 100 ng/ml of FGF-1 and after 3 days of treatment with 8 ng/ml of TGF-β1. Similarly, transcripts for FGF-2 were dramatically increased above those in control cells with TGF-β1 or FGF-1, as were those for FGF receptor-1. These results demonstrate important regulatory links between FGF-2 and both TGF-β1 and FGF-1 in the alveolar epithelium that could contribute to the regulation of normal cell turnover, development, and the repair processes after injury in the lung.

Wachstumsfaktorenkonzentration im Kulturüberstand von Keratozyten mit humanem Serum in vitro

2017 ◽  
Vol 235 (07) ◽  
pp. 840-845
Author(s):  
Nóra Szentmáry ◽  
Tanja Stachon ◽  
Ming-Feng Wu ◽  
Mona Bischoff ◽  
Manuela Huber ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Transforming Growth Factor ◽  
Keratinocyte Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
Fibroblast Growth ◽  
Fibroblast Growth Factor Basic ◽  
Hepatocyte Growth ◽  
Tgf Β1

Zusammenfassung Hintergrund Die Anwendung von Serumaugentropfen (AS) stellt eine alternative Behandlungsmethode für therapieresistente korneale Epitheldefekte dar. Bei persistierenden Epitheldefekten könnten Zytokine, die von Keratozyten im Stroma produziert werden, eine entscheidende Rolle bei der epithelialen Wundheilung spielen. Ziel dieser Studie ist es, Transforming Growth Factor β1 (TGF-β1), Keratinocyte Growth Factor (KGF), Hepatocyte Growth Factor (HGF) und Fibroblast Growth Factor basic (FGFb) im Kulturüberstand von Keratozyten mit humanem Serum (HS) in vitro zu untersuchen. Material und Methoden Serumaugentropfen von 10 Patienten wurden nach der Standardmethode der LIONS Hornhautbank Saar-Lor-Lux präpariert und bei − 80 °C tiefgefroren. Primäre humane Keratozyten wurden durch enzymatische Behandlung mit Kollagenase A (1 mg/ml) aus humanen Korneoskleralscheiben isoliert (n = 1) und in DMEM/Hamʼs Kulturmedium, versetzt mit 5% fetalem Kälberserum (FCS), kultiviert. Für den Testansatz wurden die Keratozyten mit 15 oder 30% HS (in DMEM/F14 ohne FCS) inkubiert und nach 24 h die Konzentration von TGF-β1, KGF, HGF und FGFb mittels Enzyme-linked Immunoabsorbent Assay (ELISA) aus dem Kulturüberstand bestimmt. Als Kontrolle wurden 15 oder 30% HS ohne Keratozyten nach 24 h Inkubationszeit (unter den gleichen Bedingungen wie die Keratozyten) verwendet. Ergebnisse Die HGF-Konzentration mit beiden HS-Konzentrationen war im Kulturüberstand von Keratozyten signifikant höher, im Vergleich zur HS-Kontrolle (ohne Keratozyten) nach 24 h Inkubationszeit (p < 0,01). Die FGFb-Konzentration war im Kulturüberstand mit 30% HS signifikant höher im Vergleich zur Kontrollgruppe ohne Keratozyten nach 24 Stunden Inkubationszeit (p < 0,01). Die TGF-β1- und KGF-Konzentrationen im Kulturüberstand blieben durch die Keratozyten unverändert. Schlussfolgerungen Durch die Anwesenheit von Keratozyten steigt die Konzentration von HGF und FGFb im Kulturmedium mit humanem Serum innerhalb von 24 Stunden an. Diese Konzentrationsänderungen könnten die Wundheilung bei Epitheldefekten beeinflussen.

Regulation of adipocyte precursor DNA synthesis by acidic and basic fibroblast growth factors: interaction with heparin and other growth factors

1993 ◽  
Vol 137 (3) ◽  
pp. 369-374 ◽  
Author(s):  
S. C. Butterwith ◽  
C. D. Peddie ◽  
C. Goddard
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Dna Synthesis ◽  
Fibroblast Growth Factor ◽  
Transforming Growth Factor ◽  
Fibroblast Growth ◽  
Igf I ◽  
Tgf Β1 ◽  
Adipocyte Precursor ◽  
Stimulation Of

ABSTRACT The development of adipose tissue is dependent on the growth and differentiation of fibroblast-like adipocyte precursor cells. Culture of adipocyte precursor cells in vitro has provided an ideal system for identifying potential regulators of proliferation and differentiation. We have demonstrated that both acidic fibroblast growth factor (aFGF) and basic fibroblast growth factor (bFGF) stimulate chicken adipocyte precursor DNA synthesis in a dose-dependent manner up to a concentration of 100 μg aFGF/l and 1 μg bFGF/l. The effect of bFGF was biphasic, so that in incubations with 25 μg bFGF/l, DNA synthesis was not significantly different from controls. In the presence of heparin, stimulation of DNA synthesis at 25 μg bFGF/l was 1·6-fold greater than at a concentration of 1 μg bFGF/l. Addition of heparin to incubations containing aFGF reduced the concentration required for maximum stimulation of DNA synthesis to 1 μg/l. Cells incubated with aFGF (1–100 μg/l) in combination with insulin-like growth factor-I (IGF-I), platelet-derived growth factor, transforming growth factor-α or transforming growth factor-β1 (TGF-β1) exhibited a marked synergistic increase in DNA synthesis. This was also the case when 1 μg bFGF/l was used, but at a concentration of 25 pg bFGF/l synergy was only seen with IGF-I and TGF-β1. These results suggest that both basic and acidic FGF are potentially important regulators of adipocyte hyperplasia and that their effect is modulated by constituents of the extracellular matrix and the presence of other growth factors. Journal of Endocrinology (1993) 137, 369–374

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