Disease relevance of TGFB1

• Transforming growth factor-beta 1 (TGF-beta 1) plays important roles in pathologic processes [1].
• Transforming growth factor-beta activity in sheep lung lymph during the development of pulmonary hypertension [2].
• The structural changes in the arterial walls include increased production of extracellular matrix components and smooth muscle cell hypertrophy, changes that have been similarly induced by transforming growth factor-beta (TGF-beta) in culture [2].
• TGF-beta1, a mediator of Ang II-induced fibrosis, may play a role in inducing and propagating interstitial fibrosis [3].
• At day 1, immunoreactivity for TGF-beta 1 and TGF-beta 3 proteins was seen in edema fluid, in perivascular cells associated with nonmuscular intraacinar arteries, and in alveolar walls; no increased immunoreactivity was detected for TGF-beta 2 [4].

High impact information on TGFB1

• These studies indicate that sheep lung lymph contains TGF-beta and that the level of TGF-beta increases early during the development of pulmonary hypertension [2].
• Several standard biological assays for TGF-beta activity were used for these determinations including soft agar assays, inhibition of epithelial cell proliferation, and a TGF-beta-specific radioreceptor assay [2].
• Thus, TGF-beta may contribute to the development of the structural changes in the pulmonary arteries that occur during the onset of chronic pulmonary hypertension [2].
• Serotonin mechanisms in heart valve disease I: serotonin-induced up-regulation of transforming growth factor-beta1 via G-protein signal transduction in aortic valve interstitial cells [5].
• Aortic valve endothelial cells undergo transforming growth factor-beta-mediated and non-transforming growth factor-beta-mediated transdifferentiation in vitro [6].

Chemical compound and disease context of TGFB1

• Estrogen replacement inhibits intimal hyperplasia and the accumulation and effects of transforming growth factor beta1 [7].
• The craniosynostosis was created in eight fetuses by excising their right coronal sutures, and then placing demineralized bone powder, transforming growth factor-beta, and bone morphogenetic protein-2 into the defect [8].

Biological context of TGFB1

• In addition, these sequences have been used to estimate the length of the TGF-beta 1 mRNA as 1.5-1.7 kb by Northern blot hybridization and determine that the ovine TGF-beta 1 gene occupies a single locus in the sheep genome by chromosomal in situ hybridization [1].
• Thus, the effects of TGF beta on ACTH receptor content are likely another important negative action of this peptide on adrenocortical cell differentiation [9].
• TGF-beta1 mRNA expression was significantly increased in obstructed kidneys at 109 days gestation [3].
• Transforming growth factor beta 1 inhibits fetal lamb ductus arteriosus smooth muscle cell migration [10].
• The increase in expression of TGF beta 1 and beta 2 mRNA coincidental with conceptus elongation and placental development, as well as tissue localization of the protein, suggests their involvement in early gestational development in sheep [11].

Anatomical context of TGFB1

• Up-regulation of transforming growth factor-beta1 (TGF-beta1) occurs after experimental postnatal urinary tract obstruction and we recently reported increased levels of TGF-beta1 in human renal malformations (Yang SP et al, Am J Pathol 2000, 157:1633-1647) [12].
• Basic fibroblast growth factor, transforming growth factor-beta, and platelet-derived growth factor had no effect on OAC IGFBPs [13].
• Immunoreactive TGFbeta1- like material was present in freshly isolated adrenal cells from both fetuses and newborn lambs [14].
• Taken together, these results have made TGFbeta1 a potentially attractive candidate for being an auto/paracrine negative regulator of the cholesterol side-chain cleavage system in the sheep fetal adrenal gland [14].
• In control tissue, immunohistochemical techniques localized each of the TGF-beta proteins in an identical pattern in large preacinar airways--bronchial epithelium and subepithelial cells--and in the medial wall of muscular vessels; no protein was detected in intraacinar regions [4].

Associations of TGFB1 with chemical compounds

• A 5-day treatment with TGFbeta1 (1ng/ml) decreased significantly both the cholesterol side-chain cleavage activity and the amounts of immunoreactive P450scc, adrenodoxin, and adrenodoxin reductase in sheep fetal and neonatal adrenal cells in culture [14].
• Transforming growth factor-beta inhibits steroid 17 alpha-hydroxylase cytochrome P-450 expression in ovine adrenocortical cells [15].
• Evidence is presented that this suppression was mediated by two cytokines, prostaglandin E and transforming growth factor beta, because it was reversed by multiple injections of the cyclooxygenase inhibitor indomethacin and by in vitro addition of antibody to transforming growth factor beta [16].
• TGF-beta was not found in the luminal endothelial cells at any time [17].
• Transforming growth factor-beta alone at a concentration of 1 ng/ml significantly inhibited thymidine incorporation into rat liver cells [18].

Regulatory relationships of TGFB1

• Treatment of cultured cardiac fibroblasts with transforming growth factor-beta (10 ng/ml) induced the expression of alpha-smooth muscle actin, characteristic of the transformation to myofibroblasts, and raised ANP concentrations in the medium [19].

Other interactions of TGFB1

• TGF-beta1 and eNOS levels were highest early in gestation, decreasing with maturation in both ventricles [20].
• There were also large differences in content of alpha-smooth muscle actin and transforming growth factor-beta1 between control and scalded lamb and these differences were statistically significant at day 14 (P < 0.01) [21].
• Quantitative evaluation of endothelial progenitors and cardiac valve endothelial cells: proliferation and differentiation on poly-glycolic acid/poly-4-hydroxybutyrate scaffold in response to vascular endothelial growth factor and transforming growth factor beta1 [22].
• The suppression may be due to the generation of inhibitory lymphokines, including IL-10 or transforming growth factor beta, following superantigen stimulation [23].
• Some of these cytokines, such as transforming growth factor-beta and tumor necrosis factor-alpha, promote fibrosis and repair [24].

Analytical, diagnostic and therapeutic context of TGFB1

• To further investigate the actions of this cytokine in sheep, the entire 1170-bp ovine TGF-beta 1 pro-protein-encoding sequence has been determined by the cloning and sequencing of specific polymerase-chain-reaction amplification products of TGF-beta 1 cDNA sequences [1].
• In the present study, experiments were performed to determine whether TGF-beta is present in sheep lung lymph, and whether TGF-beta levels were altered in an animal model of chronic pulmonary hypertension induced by continuous air embolization [2].
• With in situ hybridization, the three TGF-beta mRNAs co-localized in lung tissue from both control and air-embolized animals [4].
• We assessed whether transforming growth factor-beta (TGF-beta) may be responsible for the increased DA endothelial GAGs and smooth muscle FN production by confirming the presence of TGF-beta in DA tissue using immunohistochemistry and by assessing the effect of adding neutralizing antibodies to the cell cultures [25].
• Immunoprecipitation revealed TGF-beta synthesis doubled in DA versus Ao EC from 100-d gestation lambs (p < 0.05) [26].

References