Disease relevance of TGFB1

• The increase in TGF-beta s after hyperthermia could play a role in mediating the reported cardioprotective effects of heat shock [1].
• TGF-beta1 and macrophages are important regulators of tissue fibrosis and remodeling [2].
• The novel TGF-beta binding proteins have been identified in various cell lines including fetal bovine heart endothelial cells and MG-63 human osteosarcoma cells [3].
• In N-MCM, TGF-beta is found predominantly in the latent form, but in hypoxia MCM it is mainly active [4].
• Subcutaneous implantation in rats of partially purified transforming growth factor-beta (TGF-beta) derived from bovine bone induced extensive development of connective tissue with associated edema [5].

Psychiatry related information on TGFB1

• Transforming growth factor beta 1 (TGF-beta 1) has been shown to play a prominent role in controlling proteoglycan synthesis and breakdown as measured following addition to organ cultures of calf articular cartilage (Morales, T. I., and Roberts, A. B., J. Biol. Chem., 263, 12,828-12,831, 1988) [6].

High impact information on TGFB1

• Synergistic induction of mesoderm by FGF and TGF-beta and the identification of an mRNA coding for FGF in the early Xenopus embryo [7].
• Altogether, the data support the concept of a biological role for TGF-beta in the IgG-mediated negative feedback of antibody responses [8].
• In this paper, we show that transforming growth factor-beta (TGF-beta) suppresses secondary in vitro anti-sheep red blood cell responses of mouse splenocytes and lipopolysaccharide- or anti-IgM-stimulated mouse B cell responses in a way similar to, and with the same kinetics as, rodent IgG-BF [8].
• Although TGF beta 1 is normally secreted in a latent, inactive form, exposure of cultured endothelial cells to steady laminar shear stress (20 dynes/cm2) induced increased generation of biologically active TGF beta 1 [9].
• We tested the hypothesis that exposure of the endothelium to increased laminar shear stress induces the expression of TGF beta 1 via a signal transduction pathway modulated by K+ channel currents [9].

Chemical compound and disease context of TGFB1

• The proteoglycan core proteins, expressed from human cDNAs as fusion proteins with Escherichia coli maltose-binding protein, each bound TGF-beta 1 [10].
• As determined by reductions in proteinuria, glomerular planar area, and TGF-beta1 mRNA, fish oil with alpha-tocopherol ameliorated the renal injury induced by bovine gamma-globulin, whereas fish oil without alpha-tocopherol did not [11].
• CONCLUSIONS: Nicotine is a potent regulator of bFGF and TGF-beta 1 production and release by aortic SMC, and it seems to play an important role in the development and progression of atherosclerosis and neointimal fibrous hyperplasia [12].
• In this study we clarify the mode of action of RG-13577 and demonstrate that the RG-13577-induced hypertrophy is associated with an increased expression of TGF-beta1 as indicated by an increase in TGF-beta1-specific protein and mRNA level [13].
• The elevation in renal malondialdehyde content and TGF beta 1 mRNA, as well as the severity of proteinuria, was blunted by alpha-tocopherol [14].

Biological context of TGFB1

• The production of TGF-beta was variable, depending on cell density and the presence of retinoic acid [15].
• The presence of endogenously produced active TGF-beta in the culture media was shown to modulate the behavior of the cell cultures as evidenced by the effects of TGF-beta-neutralizing antisera on cell size and fibronectin production [15].
• To deduce the complete amino acid sequence of bovine TGF beta 1 we have isolated cDNA clones encoding the protein from a bovine fibropapilloma library using a human cDNA probe [16].
• Transforming growth factor-beta 1 (TGF beta 1) has been purified from a number of different sources and has a broad species specificity [16].
• The ability of inflammatory cytokine TGF-beta1 to alter endothelial cell phenotype suggests its role in the regulation of vascular endothelial cell permeability [17].

Anatomical context of TGFB1

• Our results suggest that active TGF-beta produced by airway epithelial cells may function in an autocrine or paracrine manner to modulate epithelial cell behavior [15].
• The ability of airway epithelial cells to produce transforming growth factor-beta (TGF-beta) may be an important mechanism for the control of growth, differentiation, and repair of the airway epithelium [15].
• Bovine aortic endothelial cells (BAECs) express both type I and type II receptors for transforming growth factor beta (TGF beta) [18].
• TGF-beta 2.3 inhibited proliferation of mink lung epithelial cells and promoted the formation of colonies of normal rat kidney fibroblasts in culture with specific biological activity similar to those of TGF-beta 1 and TGF-beta 2 [19].
• We demonstrate that depletion of TGF-beta1 receptor ALK5 and regulatory protein Smad4, but not ALK1 receptor attenuates TGF-beta1-induced permeability increase and significantly inhibits TGF-beta1-induced EC contraction manifested by actin stress fiber formation and increased MLC and MYPT1 phosphorylation [17].

Associations of TGFB1 with chemical compounds

• The subpopulation of heparan sulfate proteoglycans capable to bind bFGF was also largely increased after ACTH or TGF beta treatment and paralleled the variation in overall proteoheparan sulfate synthesis [20].
• Addition of anti-TGF-beta 1 antibodies, plasminogen activator inhibitor-1 (PAI-1), or the thrombin inhibitory combination of heparin and anti-thrombin III (AT III) to the cells at the time of scraping blocked about 50% of the increase in bFGF mRNA; the effects of these agents were not additive [21].
• Cross-linking experiments with disuccinimidyl suberate demonstrated the presence of two TGF beta receptor subtypes, a predominant 85 kDa form and a minor 65 kDa form [22].
• In general, STS, E2 and P4 increased TGF-beta1 expression [23].
• TGF-beta1 induced DNA synthesis was inhibited by SB 203580 or PD 98059, selective inhibitors of p38 and MAP kinase kinase (MEK), respectively [24].

Physical interactions of TGFB1

• Thus those effects of TGF beta and ACTH on proteoglycan synthesis may participate in an increased ability of adrenocortical cells to bind and respond to bFGF [20].
• Adhesion to a 60 kd tryptic fragment of fibronectin that is not involved in integrin-mediated cell binding was also increased by TGF-beta [25].

Regulatory relationships of TGFB1

• However, the inhibition by TGF beta was greatly enhanced if the cells were pretreated with TGF beta before addition of bFGF [26].
• Also, preincubation of MAC-T cells with 50 pM TGF-beta 1 or TGF-beta 2 markedly downregulated TGF-beta receptors [27].
• H7 and genistein also suppressed TGF-beta-induced TIMP-3 protein expression [28].
• The inclusion of neutralizing antibodies to TGF-beta in the co-culture medium blocked the observed increase in PAI-1 levels [29].
• TGF-beta1 potently induces VEGF receptor 1 (VEGFR-1) expression in endothelial cells and thereby prevents oxygen-induced vessel loss in vivo [30].

Other interactions of TGFB1

• Neutralizing antisera to TGF-beta 1 and TGF-beta 2 were used to demonstrate that the majority of the activity was of the TGF-beta 2 isoform [15].
• The observed increase in proteolytic activity induced by bFGF was effectively diminished by picogram amounts of transforming growth factor beta (TGF beta), but could not be abolished by increasing the amount of TGF beta [26].
• Together, the results suggest that MGP plays a role in EC function, altering the response to TGF-beta superfamily growth factors [31].
• Both bFGF and TGF beta increased the secretion of the endothelial-type plasminogen activator inhibitor [26].
• Antibodies against EGF, FGF-2, IGF-I, and PDGF did not inhibit the TGF-beta1 induced DNA synthesis [24].

Analytical, diagnostic and therapeutic context of TGFB1

• Using a bioassay, TGF-beta activity was detected readily in media conditioned by bovine bronchial epithelial cells [15].
• These cells displayed surface expression of the type III receptor protein, as determined by cross-linking with iodinated TGF beta 1 and immunoprecipitation with antibodies to the type III receptor protein [18].
• TGF-beta 2.3 eluted as a single sharp peak by reverse-phase high performance liquid chromatography [19].
• Sequence analysis of two independent cDNA clones revealed that the 112 amino acids corresponding to bovine TGF beta 1 are identical to those of the human and porcine proteins [16].
• RT-PCR, Western blot and laser scanning cytometry (LSC) were used for analysis of TGF-beta1 transcript and protein level as well as apoptosis and cell cycle in examined MEC [23].

References