Disease relevance of TGFB2

• Increased TGF-beta2 in severe asthma with eosinophilia [1].
• All skin metastases and most primary melanomas invasive to Clark's level IV-V revealed specific TGF-beta 2 mRNA and protein expression [2].
• PURPOSE: The increase in intraocular pressure in primary open-angle glaucoma (POAG) may involve transforming growth factor (TGF)-beta2 signaling, as TGF-beta2 is found in higher amounts than normal in the aqueous humor of patients with POAG [3].
• Human glioblastoma cells secrete a factor termed glioblastoma derived T cell suppressor factor (G-TsF) or transforming growth factor beta 2 (TGF-beta 2) which inhibits the response of T cells to mitogenic or antigenic stimulation [4].
• Thus, this result suggests that TGF-beta 2 may be involved in the early stages of neuronal cell degeneration in prion diseases [5].
• In spheroid and Boyden chamber migration assays, inhibition of MMP-2 activity using a specific MMP-2 inhibitor and blocking of integrin alpha(v)beta(3) abrogated glioma cell migration stimulated by TGF-beta2 [6].

Psychiatry related information on TGFB2

• The transforming growth factor-betas (TGF-betas) influence cell survival, and TGF-beta2 shows increased immunoexpression in neurofibrillary tangle-bearing neurons and reactive glia in Alzheimer's disease (AD) and progressive supranuclear palsy (PSP) [7].
• CONCLUSION: Our results show that in patients with anorexia nervosa, there are lower levels of specific cytokines (especially IL-2 and TGF-beta2) [8].
• In contrast, TGF-beta 2 was significantly decreased in CSF of CJD compared to all groups [9].

High impact information on TGFB2

• Excess TGF-beta 1 competes for binding of radioiodinated TGF-beta 1 in a dose-dependent manner and is more effective than TGF-beta 2 [10].
• A 280 kd receptor displays high affinity for both TGF-beta 1 and TGF-beta 2 [11].
• Retinoblastoma gene product activates expression of the human TGF-beta 2 gene through transcription factor ATF-2 [12].
• The human TGF-beta 2 promoter contains multiple elements including an ATF site, which is essential for basal promoter activity [12].
• Our results reveal a new mechanism by which pRb constrains cellular proliferation: by activating expression of the inhibitory growth factor, TGF-beta 2 [12].

Chemical compound and disease context of TGFB2

• This is the first report which demonstrates that norethindrone stimulates estrogen-responsive human breast cancer cell growth and inhibits the expression of TGF beta 2 and TGF beta 3 mRNAs [13].
• Mean TGF beta 1 plasma levels in the ANCA associated vasculitis (AAV) patients ranged from 8.9 (Wegeners granulomatosis, WG) to 13.3 ng/ml (Churg-Strauss syndrome, CSS)(control: 4.2 ng/ml, p < 0.01) while TGF beta 2 levels were not elevated [14].
• We investigated whether inhibition of TGF-beta2, which is overexpressed in LCC2 tamoxifen-resistant human breast cancer cells, could modify antiestrogen resistance [15].
• Finally, tranilast administered orally inhibited the growth of experimental 9L rat gliomas and reduced expression of TGF-beta2 in vivo [16].
• METHODS: The effect of daily administration of TGF-beta2 on tissue vasoconstriction, tissue levels of endothelin and angiotensin II, tissue hypoxia, and renal fibrosis were examined [17].

Biological context of TGFB2

• Finally, utilizing the polymorphisms described for TGFB2 and HLX1, we have been able to localize these genes within a framework map of the distal long arm of chromosome 1 and to study the linkage relationship between these two genes [18].
• We propose that HLX1 is the human homologue of the mouse homeobox gene Hlx based on extensive sequence homology between the genes and the close proximity of both genes to TGFB2 in their respective species [18].
• Transfection of these cells with TbetaRII-B restores TGF-beta2 sensitivity [19].
• While signal transduction by TGF-beta1 has been well characterized, receptor binding and activation by the TGF-beta2 isoform is less well understood [19].
• Recently, the TbetaRIII null mouse was generated and revealed significant non-overlapping phenotypes with the TGF-beta2 null mouse, implying the existence of TbetaRIII independent mechanisms for TGF-beta2 signaling [20].

Anatomical context of TGFB2

• Expressed alone in COS-7 cells the type II receptor also cannot bind TGF-beta 2; co-expression of type III receptor enables the type II receptor to bind TGF-beta 2 [21].
• CONCLUSION: TGF-beta2, expressed mainly by eosinophils, is the predominant isoform expressed in severe asthma, and is associated with increased profibrotic responses [1].
• All the cell lines expressed TGF-beta 1, but TGF-beta 2 and TGF-beta 3 mRNA levels were variable [22].
• Interferon-gamma differentially regulates TGF-beta1 and TGF-beta2 expression in human retinal pigment epithelial cells through JAK-STAT pathway [23].
• TGF-beta 2 and TGF-beta 3 immunoreactivity within the ciliary epithelium [corrected] [24].

Associations of TGFB2 with chemical compounds

• Transforming growth factor beta isoforms (TGF-beta 1 and TGF-beta 2) inhibited sulfate incorporation into proteoglycans in a dose-dependent manner [25].
• On the other hand, NAC was capable of counteracting the LPS-induced inhibition of TGF-beta2 expression [26].
• TGF-beta2 mRNA level was decreased by LPS and was not changed in the presence of L-NMMA [26].
• TGF-beta 2 induction was only weakly enhanced by cycloheximide and was completely inhibited by actinomycin D [27].
• The 38-kDa TGF-beta binding component, an N-linked glycoprotein, exhibits a higher affinity for TGF-beta 2 than for -beta 1 that is strikingly similar to that of the type III/betaglycan receptor [28].

Physical interactions of TGFB2

• In contrast, 125I-TGF-beta 2 cannot bind and be chemically cross-linked to the soluble type II receptor, nor does as much as a 125-fold excess of unlabeled TGF-beta 2 inhibit the binding of 125I-TGF-beta 1 to the soluble receptor [21].
• Competition affinity-labeling experiments showed that endoglin binds TGF-beta 1 (KD approximately 50 pM) and TGF-beta 3 with high affinity but fails to bind TGF-beta 2 [29].
• Our studies also indicate that PZP binds TGF-beta 2 with higher affinity than TGF-beta 1 [30].
• Here we report that in addition to the free form of TGF beta 2, a stable complex between a approximately 110 kDa binding protein and TGF beta 2 was isolated from glioblastoma cell supernatant [31].
• Interestingly, TGF-beta 2 delayed the nuclear transport of syndecan-1 concomitantly with an antiproliferative effect [32].

Co-localisations of TGFB2

• The authors anticipated TGF-beta 3 immunoreactivity because TGF-beta 3 often co-localizes with TGF-beta 2 [24].

Regulatory relationships of TGFB2

• IL-4 and IL-13 both stimulated production of TGF-beta2 release from human bronchial epithelial cells in a time- and concentration-dependent manner [33].
• TGF-beta1 stimulated TGF-beta2 production (p < 0.01 relative to control) [34].
• TGF-beta 1 and TGF-beta 2 upregulated the FN release in a dose- and time-dependent manner [35].
• Forkhead factor FKHRL1 binds in vitro to the three consensus sequences and can activate TGF-beta2 promoter in normal and Akt-transformed cell lines [36].
• These results suggest that IFN-gamma down regulates TGF-beta2 production by HBECs by regulating Smad 7 [37].

Other interactions of TGFB2

• Here, we show that TbetaRII-B, an alternatively spliced variant of the TGF-beta type II receptor, is a TGF-beta2 binding receptor, which mediates signalling via the Smad pathway in the absence of any TGF-beta type III receptor (TbetaRIII) [19].
• The gene for transforming growth factor beta 2 (TGFB2) and the gene for the homeodomain box (HLX1) are both eliminated as candidates for USH2A, by virtue of their localization outside these flanking markers [38].
• TGF beta1, TGF beta2, and TGF beta3 were strongly positive in all 15 patients, but only scattered cells were positive in the normal controls [39].
• IFN-gamma reduced the production of active form of TGF-beta2 to 4-9% [23].
• RT-PCR analyses showed that TNF-alpha and IL-1beta increased the mRNA levels of both TGF-beta1 and TGF-beta2 [23].

Analytical, diagnostic and therapeutic context of TGFB2

• The expression and localization of TGF-beta1, TGF-beta2, TGF-beta3, TbetaR-IALK5, TbetaR-II, and TbetaR-III were studied by Northern blot analysis, in situ hybridization, and immunohistochemistry [40].
• Northern blotting showed expression of TGF beta 1 mRNA in ten, TGF beta 2 mRNA in two and TGF beta 3 mRNA in seven cell lines [41].
• Sequence analysis of the promoter region of the glioblastoma derived T cell suppressor factor/transforming growth factor (TGF)-beta 2 gene reveals striking differences to the TGF-beta 1 and -beta 3 genes [4].
• ELISA was used to determine TGF-beta1 and TGF-beta2 proteins in the media [42].
• HPMCs constitutively released appreciable amounts of TGF-beta 1 and low amounts of TGF-beta 2 as detected by specific immunoassays [43].

References