The expression of transforming growth factor-β by cultured chick growth plate chondrocytes: differential regulation by 1,25-dihydroxyvitamin D3

1996 ◽  
Vol 149 (2) ◽  
pp. 277-285 ◽  
Author(s):  
C Farquharson ◽  
A S Law ◽  
E Seawright ◽  
D W Burt ◽  
C C Whitehead
Keyword(s):  
Growth Factor ◽  
Conditioned Medium ◽  
Growth Plate ◽  
Bone Growth ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Mrna Levels ◽  
Chick Growth ◽  
Growth Plate Chondrocytes ◽  
Tgf Β1

Abstract 1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) and transforming growth factor-β (TGF-β) are both important regulators of chondrocyte growth and differentiation. We report here that 1,25(OH)2D3 differentially regulates the expression of the genes for TGF-β1 to -β3 and the secretion of the corresponding proteins in cultured chick chondrocytes. Confluent growth plate chondrocytes were serum-deprived and cultured in varying concentrations of 1,25(OH)2D3. Cells were assayed for TGF-β mRNA and conditioned medium was assayed for TGF-β activity and isoform composition. Active TGF-β was only detected in 10−8m 1,25(OH)2D3-treated cultures (8·37 ng active TGF-β/mg protein). There was a significant decrease in total (latent+active) TGF-β activity in conditioned medium of 10−12 m (23·4%; P<0·05) and 10−10 m (20·7%; P<0·05) 1,25(OH)2D3-treated cultures but 10−8 m 1,25(OH)2D3 significantly increased (30·9%; P<0·01) TGF-β activity. The amounts of TGF-β1, -β2 and -β3 isoforms produced were similar in control, 10−10 or 10−12m 1,25(OH)2D3-treated cultures but the conditioned medium of 10−8 m 1,25(OH)2D3-treated cultures contained significantly higher amounts of all three isoforms. Quantification of TGF-β mRNA demonstrated differential control of TGF-β gene expression with TGF-β1 and -β3 mRNA levels reduced by all concentrations of 1,25(OH)2D3 examined (10−8, 10−10 and 10−12 m) whilst TGF-β2 mRNA concentrations were elevated. Our results indicated that 1,25(OH)2D3 regulates chick growth plate chondrocyte TGF-β secretion and mRNA expression in a concentration-dependent and isoform-specific manner. This interaction may be important in the regulation of chondrocyte metabolism and endochondral bone growth. Journal of Endocrinology (1996) 149, 277–285

Effects of Transforming Growth Factor-β on Matrix Synthesis by Chick Growth Plate Chondrocytes*

Endocrinology ◽  
1988 ◽  
Vol 122 (6) ◽  
pp. 2953-2961 ◽  
Author(s):  
REGIS J. O’KEEFE ◽  
J. EDWARD PUZAS ◽  
JOHN S. BRAND ◽  
RANDY N. ROSIER
Keyword(s):  
Growth Factor ◽  
Growth Plate ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Chick Growth ◽  
Matrix Synthesis ◽  
Growth Plate Chondrocytes

scholarly journals Increased Expression of Transforming Growth Factor-β after Cerebral Ischemia in the Baboon: An Endogenous Marker of Neuronal Stress?

2001 ◽  
Vol 21 (7) ◽  
pp. 820-827 ◽  
Author(s):  
Carine Ali ◽  
Fabian Docagne ◽  
Olivier Nicole ◽  
Sylvain Lesné ◽  
Jérôme Toutain ◽  
...  
Keyword(s):  
Growth Factor ◽  
Nonhuman Primate ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Oxygen Metabolism ◽  
Artery Occlusion ◽  
Experimental Stroke ◽  
Mrna Levels ◽  
Primate Model ◽  
Tgf Β1

There has been an increasing interest in recent years in the evaluation of the neuronal and glial responses to ischemic insult. Some cytokines, including transforming growth factor-β (TGF-β), that are overexpressed after experimental stroke in rodents are thought to be implicated in the neuronal processes that lead to necrosis. Thus, such cytokines could predict tissue fate after stroke in humans, although data are currently sparse for gyrencephalic species. The current study addressed the expression pattern of TGF-β1 in a nonhuman primate model of middle cerebral artery occlusion. Focal permanent ischemia was induced for 1 or 7 days in 6 baboons and the following investigations were undertaken: cerebral oxygen metabolism (CMRO2) positron emission tomography studies, magnetic resonance imaging, postmortem histology, and reverse transcription-polymerase chain reaction. The aim of the current study was to correlate the expression of TGF-β1 to the underlying metabolic and histologic state of the threatened cerebral parenchyma. The authors evidenced increased TGF-β1 mRNA levels (up to 25-fold) in those regions displaying a moderate (20% to 49%) reduction in CMRO2. The current findings suggest that the greatly enhanced expression of TGF-β1 in the penumbral zones that surround tissue destined to infarction may represent a robust index of potentially salvageable brain. The current investigation, in the nonhuman primate, strengthens the authors' hypothesis, derived from rodent models, that TGF-β1 may be involved in the physiopathology of human stroke.

Co-activation of synovial fibroblasts by laminin-111 and transforming growth factor-β induces expression of matrix metalloproteinases 3 and 10 independently of nuclear factor-κB

2007 ◽  
Vol 67 (4) ◽  
pp. 559-562 ◽  
Author(s):  
K Warstat ◽  
T Pap ◽  
G Klein ◽  
S Gay ◽  
W K Aicher
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Synovial Fibroblasts ◽  
Transforming Growth Factor Β ◽  
Nuclear Factor Κb ◽  
Mrna Levels ◽  
Nuclear Factor ◽  
The Matrix ◽  
Specific Tissue ◽  
Significant Expression

We showed previously that the attachment of synovial fibroblasts to laminin (LM)-111 in the presence of transforming growth factor-β induces significant expression of the matrix metalloproteinase (MMP)-3. Here we go on to investigate the regulation of additional MMPs and their specific tissue inhibitors of matrix proteases (TIMPs). Changes in steady-state mRNA levels encoding TIMPs and MMPs were investigated by quantitative reverse transcription–polymerase chain reaction. Production of MMPs was monitored by a multiplexed immunoarray. Signal transduction pathways were studied by immunoblotting. Attachment of synovial fibroblasts to LM-111 in the presence of transforming growth factor-β induced significant increases in MMP-3 mRNA (12.35-fold, p<0.001) and protein (mean 62 ng/ml, sixfold, p<0.008) and in expression of MMP-10 mRNA (11.68-fold, p<0.05) and protein (54 ng/ml, 20-fold, p⩾0.02). All other TIMPs and MMPs investigated failed to show this LM-111-facilitated transforming growth factor-β response. No phosphorylation of nuclear factor-κB was observed. We conclude that co-stimulation of synovial fibroblasts by LM-111 together with transforming growth factor-β suffices to induce significant expression of MMP-3 and MMP-10 by synovial fibroblasts and that this induction is independent of nuclear factor-κB phosphorylation.

scholarly journals Analytical Characterization of an Enzyme-Linked Immunosorbent Assay for the Measurement of Transforming Growth Factor β1 in Human Plasma

2018 ◽  
Vol 3 (2) ◽  
pp. 200-212 ◽  
Author(s):  
Brendan M Giles ◽  
Timothy T Underwood ◽  
Karim A Benhadji ◽  
Diana K S Nelson ◽  
Lisa M Grobeck ◽  
...  
Keyword(s):  
Growth Factor ◽  
Human Plasma ◽  
Patient Selection ◽  
Transforming Growth Factor ◽  
Sandwich Elisa ◽  
Transforming Growth Factor Β ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Individuals ◽  
Tgf Β1 ◽  
Apparently Healthy

Abstract Background The transforming growth factor β (TGF-β)–signaling pathway has emerged as a promising therapeutic target for many disease states including hepatocellular carcinoma (HCC). Because of the pleiotropic effects of this pathway, patient selection and monitoring may be important. TGF-β1 is the most prevalent isoform, and an assay to measure plasma levels of TGF-β1 would provide a rational biomarker to assist with patient selection. Therefore, the objective of this study was to analytically validate a colorimetric ELISA for the quantification of TGF-β1 in human plasma. Methods A colorimetric sandwich ELISA for TGF-β1 was analytically validated per Clinical and Laboratory Standards Institute protocols by assessment of precision, linearity, interfering substances, and stability. A reference range for plasma TGF-β1 was established for apparently healthy individuals and potential applicability was demonstrated in HCC patients. Results Precision was assessed for samples ranging from 633 to 10822 pg/mL, with total variance ranging from 28.4% to 7.2%. The assay was linear across the entire measuring range, and no interference of common blood components or similar molecules was observed. For apparently healthy individuals, the average TGF-β1 level was 1985 ± 1488 pg/mL compared to 4243 ± 2003 pg/mL for HCC patients. Additionally, the TGF-β1 level in plasma samples was demonstrated to be stable across all conditions tested, including multiple freeze–thaw cycles. Conclusions The ELISA described in this report is suitable for the quantification of TGF-β1 in human plasma and for investigational use in an approved clinical study.

scholarly journals The expression of transforming growth factor β in pregnant rat myometrium is hormone and stretch dependent

Reproduction ◽  
2007 ◽  
Vol 134 (3) ◽  
pp. 503-511 ◽  
Author(s):  
Oksana Shynlova ◽  
Prudence Tsui ◽  
Anna Dorogin ◽  
B Lowell Langille ◽  
Stephen J Lye
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Late Gestation ◽  
Quiescent State ◽  
Mrna Levels ◽  
Pregnant Rats ◽  
Pregnant Rat ◽  
Threefold Increase ◽  
Antagonist Ru486

From a quiescent state in early pregnancy to a highly contractile state in labor, the myometrium displays tremendous growth and remodeling. We hypothesize that the transforming growth factor β (TGFβ) system is involved in the differentiation of pregnant myometrium throughout gestation and labor. Furthermore, we propose that during pregnancy the mechanical and hormonal stimuli play a role in regulating myometrial TGFβs. The expression of TGFβ1-3 mRNAs and proteins was examined by real-time PCR, Western immunoblot, and localized with immunohistochemistry in the rat uterus throughout pregnancy and labor. Tgfβ1-3 genes were expressed differentially in pregnant myometrium. Tgfβ2 gene was not affected by pregnancy, whereas the Tgfβ1 gene showed a threefold increase during the second half of gestation. In contrast, we observed a dramatic bimodal change in Tgfβ3 gene expression throughout pregnancy. Tgfβ3 mRNA levels first transiently increased at mid-gestation (11-fold on day 14) and later at term (45-fold at labor, day 23). Protein expression levels paralleled the changes in mRNA. Treatment of pregnant rats with the progesterone (P4) receptor antagonist RU486 induced premature labor on day 19 and increased Tgfβ3 mRNA, whereas artificial maintenance of elevated P4 levels at late gestation (days 20–23) caused a significant decrease in the expression of Tgfβ3 gene. In addition, Tgfβ3 was up-regulated specifically in the gravid horn of unilaterally pregnant rats subjected to a passive biological stretch imposed by the growing fetuses, but not in the empty horn. Collectively, these data indicate that the TGFβ family contributes in the regulation of myometrial activation at term integrating mechanical and endocrine signals for successful labor contraction.

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