scholarly journals Vascular Endothelial Growth Factor Is Regulated by the Canonical and Noncanonical Transforming Growth Factor-β Pathway in Synovial Fibroblasts Derived from Osteoarthritis Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Shotaro Takano ◽  
Kentaro Uchida ◽  
Shintaro Shoji ◽  
Makoto Itakura ◽  
Dai Iwase ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Mrna Expression ◽  
Protein Production ◽  
Transforming Growth Factor ◽  
Synovial Fibroblasts ◽  
Vascular Endothelial ◽  
P38 Inhibitor ◽  
Endothelial Growth Factor ◽  
Vegf Protein

Background. Previous studies suggest the presence of an association of vascular endothelial growth factor (VEGF) with osteoarthritis (OA) severity and pain in patients with knee OA. VEGF expression in human synovial fibroblasts (SFs) is induced by transforming growth factor-beta (TGFβ). However, the signaling pathway governing TGFβ-mediated regulation of VEGF in SFs has not been identified. Methods. OA patients who underwent total knee arthroplasty had their synovial tissue (SYT) extracted and the constituent SFs cultured. The cells were stimulated with culture medium (control), human recombinant TGFβ (hrTGFβ), hrTGFβ + ALK5 inhibitor SB505124, hrTGFβ + transforming growth factor activating kinase 1 (TAK1) inhibitor (5Z)-7-oxozeaenol, or hrTGFβ + p38 inhibitor SB203580 for 6 h. VEGF mRNA expression in SFs was examined using real-time polymerase chain reaction and VEGF protein production in the cell supernatant was examined using enzyme-linked immunosorbent assay. Additionally, phosphorylated levels of SMAD2 and p38 were examined using western blotting. Results. ALK5 (SB505124) and TAK1 (5Z-oxozeaenol) inhibitors completely suppressed TGFβ-induced VEGF mRNA expression and VEGF protein production. Both SB505124 and 5Z-oxozeaenol also suppressed SMAD2 and p38 phosphorylation. The p38 inhibitor (SB203580) partially inhibited TGFβ-mediated VEGF mRNA and VEGF protein production. Conclusion. TGFβ-mediated regulation of VEGF expression and VEGF protein production in the SYT of OA patients occurs through both the canonical and noncanonical pathway.

scholarly journals Expression and localisation of vascular endothelial growth factor and basic fibroblast growth factor during the final growth of bovine ovarian follicles

2000 ◽  
Vol 167 (3) ◽  
pp. 371-382 ◽  
Author(s):  
B Berisha ◽  
D Schams ◽  
M Kosmann ◽  
W Amselgruber ◽  
R Einspanier
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Mrna Expression ◽  
Regulatory Change ◽  
Vascular Endothelial ◽  
Fibroblast Growth ◽  
Follicle Growth ◽  
Preovulatory Follicles ◽  
Endothelial Growth Factor ◽  
Vegf Protein

Locally produced growth factors may have important modulatory roles in final ovarian follicular growth. The aim of this study was to investigate the possible participation of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF2) in bovine follicles during final growth. Ovaries were collected from a slaughterhouse within 10-20 min after exsanguination. A classification of follicles into five groups (<0.5; >0.5-5; >5-20; >20-180; >180 ng/ml) was performed according to the follicular fluid (FF) oestradiol-17 beta content. For a better characterisation of classes the mRNA expressions of FSH receptor, LH receptor and aromatase cytochrome P450 in theca interna (TI) and granulosa cells (GC) were determined. Analysis of VEGF transcript by RT-PCR showed that GC and theca cells express predominantly the smallest isoforms (VEGF(121) and VEGF(165)). VEGF mRNA expression in both tissues (TI and GC) and VEGF protein concentration in total follicle tissue increased significantly (and correlated) with developmental stages of follicle growth. The expression of mRNA for VEGF receptor (VEGFR)-1 and VEGFR-2 was very weak in GC, without any regulatory change during final follicle growth. In contrast, TI showed strong expression of mRNA for both receptors in all follicle classes examined. VEGF protein concentrations in FF increased significantly and continuously to maximum levels in preovulatory follicles. As shown by immunohistochemistry, VEGF protein was clearly localised in TI and GC of preovulatory follicles. FGF2 and FGF receptor (FGFR) mRNA expression in TI increased significantly during final growth of follicles. In contrast, the FGF2 and FGFR mRNA expression in GC was very weak and without any regulatory change during follicle growth. Histological observation revealed that FGF2 protein was localised in theca tissue (cytoplasm of endothelial cells and pericytes) but not in GC. Our results suggest that VEGF and FGF families are involved in the proliferation of capillaries that accompanies the selection of the preovulatory follicle resulting in an increased supply of nutrients and precursors, and therefore supporting the growth of the dominant follicle.

Differentiated human podocytes endogenously express an inhibitory isoform of vascular endothelial growth factor (VEGF165b) mRNA and protein

2004 ◽  
Vol 286 (4) ◽  
pp. F767-F773 ◽  
Author(s):  
Tai-Gen Cui ◽  
Rebecca R. Foster ◽  
Moin Saleem ◽  
Peter W. Mathieson ◽  
David A. Gillatt ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Protein Concentration ◽  
Protein Production ◽  
No Reduction ◽  
Cancer Therapies ◽  
Vascular Endothelial ◽  
Rt Pcr ◽  
Endothelial Growth Factor ◽  
Vegf Protein

Despite production by podocytes of the proangiogenic molecule vascular endothelial growth factor-A (VEGF), the glomeruli are not sites of angiogenesis. We recently described mRNA expression of an inhibitory splice variant of VEGF (VEGF165b) in normal kidney (Bates DO, Cui TG, Doughty JM, Winkler M, Sugiono M, Shields JD, Peat D, Gillatt D, and Harper SJ. Cancer Res 62: 4123–4131, 2002). Available anti-VEGF antibodies do not distinguish stimulatory from inhibitory VEGF families. To assess the production of VEGF165 (stimulatory) and VEGF165b (inhibitory) isoforms by human podocytes, we examined both primary cultured and conditionally immortalized human podocytes using family- and isoform-specific RT-PCR. In addition, VEGF protein production was analyzed in podocytes, using isoform-specific double-strand small-interference RNAs (siRNA). RT-PCR demonstrated the production of VEGF189 mRNA by podocytes of both phenotypes. In contrast, on differentiation there was a splicing change from VEGF165 to VEGF165b mRNA. In addition, VEGF protein in the supernatant of conditionally immortalized, differentiated podocytes was reduced by VEGF165b siRNA to 20 ± 11% of the level of mock-transfected cells ( P < 0.01). No reduction was seen with mismatch siRNA. Moreover, there was no reduction in VEGF protein concentration in the supernatant of primary cultured, dedifferentiated human podocytes (109 ± 8% of mismatch siRNA, P > 0.1). In conclusion, differentiated but not dedifferentiated human podocytes secrete significant amounts of VEGF165b protein. It is possible that this may explain the paradox of high VEGF production in the glomerulus but no angiogenesis. Furthermore, the existence of this splicing switch in relation to podocyte phenotype suggests that alternative splicing of the VEGF pre-RNA is a regulated process that is open to manipulation and therefore could be a target for novel cancer therapies.

Vascular Endothelial Growth Factor Level Correlates With Transforming Growth Factor-β Isoform Levels in Pleural Effusions

CHEST Journal ◽  
2000 ◽  
Vol 118 (6) ◽  
pp. 1747-1753 ◽  
Author(s):  
Dong-sheng Cheng ◽  
Y. C. Gary Lee ◽  
Jeffrey T. Rogers ◽  
Elizabeth A. Perkett ◽  
J. Philip Moyers ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Vascular Endothelial ◽  
Pleural Effusions ◽  
Factor Level ◽  
Endothelial Growth Factor

scholarly journals Angiogenic and Inflammatory Properties of Psoriatic Arthritis

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Toshiyuki Yamamoto
Keyword(s):  
Psoriatic Arthritis ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Synovial Fibroblasts ◽  
Osteoclast Formation ◽  
Endothelial Cell Migration ◽  
Vascular Endothelial ◽  
Inflammatory Arthropathy ◽  
Synovial Tissues ◽  
Endothelial Growth Factor

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy associated with psoriasis and included in seronegative spondyloarthropathy. PsA has several unique characteristics different from rheumatoid arthritis (RA), such as enthesopathy, dactylitis, and abnormal bone remodeling. As compared with synovitis of RA (pannus), proliferation of PsA synovium is mild and characterized by hypervascularity and increased infiltration of polymorphonuclear leukocytes in the synovial tissues. Angiogenesis plays a crucial role in cutaneous psoriasis, and several angiogenic factors such as vascular endothelial growth factor, interleukin-8, angiopoietin, tumor necrosis factor-α and transforming growth factor-β, are suggested to play an important role also in the pathophysiology of PsA. Further, IL-17 has various functions such as upregulation of proinflammatory cytokines, attraction of neutrophils, stimulation of keratinocytes, endothelial cell migration, and osteoclast formation via RANKL from activated synovial fibroblasts. Thus, IL-17 may be important in angiogenesis, fibrogenesis, and osteoclastogenesis in PsA. In this paper, roles of angiogenesis in the psoriatic synovium are discussed, which may strengthen the understanding of the pathogenesis of PsA.

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