Disease relevance of Tgfbr2

• We evaluated the correlation of arterial proliferation with plasma levels of TGF-beta 1 and TGF-beta receptor type II, respectively, in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a new strain of spontaneous non-insulin-dependent diabetes mellitus (NIDDM) models [1].
• Suppression of in vivo tumorigenicity of rat hepatoma cell line KDH-8 cells by soluble TGF-beta receptor type II [2].
• During the process of neovascularization, immunoreactivity and mRNA expression of TbetaRI and TbetaRII were widely distributed in laser lesions soon after photocoagulation; thereafter, these receptors were specifically detected in the endothelial cells of choroidal neovascularization [3].
• RESULTS: In normal adult rat retinas, immunoreactivity and mRNA expression of TGF-beta receptor type I (TbetaRI) and TGF-beta receptor type II (TbetaRII) were found in the ganglion cells [3].

High impact information on Tgfbr2

• We have previously shown that transforming growth factor beta 1 (TGF-beta 1) receptor and TGF-beta type II receptor (T beta R-II) are produced in lactotropes, and that TGF-beta 1 inhibits the growth of these anterior pituitary cells by an autocrine mechanism [4].
• Moreover, down-regulating the TGF-beta receptor type II by the siRNA technique or antagonizing the S1P(3) receptor subtype with suramin abrogates S1P-stimulated Smad phosphorylation [5].
• The glomerular TGF-beta Type II Receptor mRNA and protein concentrations increased over 30 days in untreated diabetic animals compared with non-diabetic controls, while enalapril-treated diabetic animals showed a normalisation of TGF-beta Type II Receptor mRNA and protein [6].
• Cultured aortic smooth muscle cells of diabetic rats expressed TGF-beta type II receptor about 8.7 times that of controls at the protein level and 5.7 times at the mRNA level, whereas the expression of the type I receptor did not differ between the two types of smooth muscle cells [7].
• We now show that the neurons generated by TGFbeta factors belong to the autonomic lineage and that cells within the developing sympathetic ganglia express TGFbeta-type II receptor [8].

Biological context of Tgfbr2

• RNA blot hybridization and reverse-transcription polymerase chain reaction (RT-PCR) analyses showed that rat TGF-beta type II receptor is widely distributed in various tissues and is expressed abundantly in the ovary and lung [9].
• Transforming growth factor (TGF)-beta1 is an important apoptotic growth inhibitor of hepatocyte proliferation, and the expression of TGF-beta1, which regulates cell proliferation, is closely associated with the expression level of TGF-beta type II receptor (TGR2) [10].
• The peak levels of gene expression of TGFbeta-1, TGFR-1 and TGFR-2 in the fibroblasts treated with SP were achieved at 6 and 12 hours, respectively [11].

Anatomical context of Tgfbr2

• Immunoreactive TGF-beta receptor type II antigen was detected by immunohistochemistry on the thoracic artery [1].
• We first stably transfected rat glomerular mesangial cells with a kinase-deleted mutant TGF-beta type II receptor (TbetaR-II(M)) designed to inhibit TGF-beta(1) signaling in a dominant-negative fashion [12].
• As vascular development progressed, TGF-beta type II receptor, alpha-smooth muscle actin and renin immunoreactivity became progressively restricted to small renal arteries and arterioles [13].
• Intense TGF-beta type II receptor expression in renal stromal vascular smooth muscle cell precursors and developing blood vessels suggests a role for the TGF-beta type II receptors in the formation of the renal vascular smooth muscle compartment [13].
• On gestational day 17 TGF-beta type II receptor immunoreactive stromal cells were observed within the kidney, with the same distribution as stromal alpha-smooth muscle actin and renin immunoreactive cells, and intense stromal TGF-beta type II receptor immunoreactivity continued through postnatal day 5 [13].

Associations of Tgfbr2 with chemical compounds

• Dopamine, dopamine D2 receptor short isoform, transforming growth factor (TGF)-beta1, and TGF-beta type II receptor interact to inhibit the growth of pituitary lactotropes [14].
• The rat TGF-beta type II receptor comprises 567 amino acid residues with a cysteine-rich extracellular domain, a single transmembrane domain and an intracellular protein kinase domain with predicted serine/threonine specificity [9].
• Prolonged curcumin treatment (>6 h) significantly reduced TGF-beta receptor type II levels and SMAD2/3 phosphorylation in response to added TGF-beta [15].
• We show here that the transforming growth factors -beta2 and -beta3 (TGF-beta) and the TGF-beta type II receptor are expressed in the embryonic rat raphe, when 5-HT neurons develop and differentiate [16].
• However, the expression of TGF-beta receptor type II under 20 mM glucose was significantly increased, but that of the TGF-beta receptor type I was not [17].

Regulatory relationships of Tgfbr2

• SHR-derived VSMC show the distinct expression and abnormal regulation by Ang II of TGF-beta receptors when compared with cells from WKY rats, which express TGF-beta type II receptor predominantly to induce PDGF A-chain stimulation of VSMC growth [18].

Other interactions of Tgfbr2

• There was also a marked increase in GEC immunostaining for TGF-beta receptor type I (T beta IR) and TGF-beta receptor type II (T beta IIR) at all time points in PHN. mRNA levels for both receptors increased at day 5 [19].
• AIM: Initial report on the in situ examination of the mRNA expression of transforming growth factor betas (TGFbetas), TGFbeta type II receptor (TbetaRII) and telomerase activity in the experimental rat liver tissue during cholangiocarcinogenesis [20].
• METHODS AND RESULTS: Overexpression of a kinase-deficient TGFbeta type II receptor (TGFbetaRIIDeltaKD) resulted in a 2.8-fold increase in cardiomyocyte DNA synthesis in serum-rich cultures, an effect requiring active FGFR-1 since it was not observed in the presence of excess kinase-deficient FGFR-1 [21].
• These observations suggest that the increased expression of the TGF-beta receptor type II via PKC-beta plays an important role in the accelerated proliferation of SMCs under a high glucose condition, leading to the development of diabetic macroangiopathy [17].
• T beta R-II was more widely distributed in cells than T beta R-III, but T beta R-III was extensively localized in the extracellular matrix [22].

Analytical, diagnostic and therapeutic context of Tgfbr2

• In situ hybridization was used to examine the TGFbetas) and TGFbeta type II receptor (TbetaRII) mRNA, in situ TRAP was used to check the telomerase activity in the tissue samples [20].
• Northern blot analysis further detected TGF-beta type II receptor (T beta R-II) mRNA transcript in addition to the above-identified receptors [23].
• Expression of mRNA for TGF-RI and TGF-RII was demonstrated in sham operated, obstructed and contralateral unobstructed kidneys using PCR [24].

References