Disease relevance of Tgfb3

• Temporal and spatial expression of Pax9 and Sonic hedgehog during development of normal mouse palates and cleft palates in TGF-beta3 null embryos [1].
• Unlike other null mutants with cleft palate, TGF-beta 3-/- mice lack other concomitant craniofacial abnormalities [2].
• TGF-beta 1 is implicated in the pathogenesis of pulmonary fibrosis, but the role of TGF-beta 2 and TGF-beta 3 remains unclear [3].
• Transforming growth factor-beta 1 (TGF-beta 1) and beta 3 (TGF-beta 3) mRNA levels were elevated in the ras + myc-induced carcinomas when compared to the normal controls or to the epithelial hyperplasias [4].
• Since TGF-beta 3 has been implicated in wound healing, we therefore hypothesized that TGF-beta 3 functions to reduce scarring after cleft lip repair [5].

High impact information on Tgfb3

• Abnormal lung development and cleft palate in mice lacking TGF-beta 3 indicates defects of epithelial-mesenchymal interaction [2].
• This study demonstrates an essential function for TGF-beta 3 in the normal morphogenesis of palate and lung, and directly implicates this cytokine in mechanisms of epithelial-mesenchymal interaction [2].
• TGF-beta 1, TGF-beta 2, and TGF-beta 3 are expressed in distinct but overlapping patterns in the developing mouse mammary gland [6].
• In the present study, we determined to establish the role of TGF-beta2 and TGF-beta3 in mediating apoptosis in non-neuronal tissue by analyzing the intestinal mucosa of Tgfbeta2(+/-) and Tgfbeta3(+/-) heterozygous mice [7].
• Immunohistochemical localization of TGF beta 1, TGF beta 2, and TGF beta 3 in the mouse embryo: expression patterns suggest multiple roles during embryonic development [8].

Chemical compound and disease context of Tgfb3

• Taken together, these data for the first time demonstrated a role for RA-induced hypochondrogenesis through regulation of the TGF-beta3 pathway and suggested a role for TbetaRII /Smad in retinoid-induced cleft palate [9].
• The present study investigated the changes in expression of two TGF-beta isoforms, TGF-beta1 and TGF-beta3, in C57BL/6 and TCR transgenic (T/R+) B10.PL mice that manifested or were protected against clinical signs of experimental autoimmune encephalomyelitis (EAE) with 17beta-estradiol (E2) treatment [10].
• Effect of ormeloxifene on ovariectomy-induced bone resorption, osteoclast differentiation and apoptosis and TGF beta-3 expression [11].

Biological context of Tgfb3

• An alternative interpretation is that the delayed expression of Tgfb2 and Tgfb3 that occurs in the absence of transforming growth factor-beta1 results in the delayed wound healing, suggesting that transforming growth factor-beta2 and/or transforming growth factor-beta3 play important parts in wound healing [12].
• One was mapped to the central region of mouse chromosome 12 between D12Mit4 and D12Mit5, near fos and Tgfb3 [13].
• Together, the results clearly demonstrate that TGF-beta2 and TGF-beta3 are essential signals for differentiation of midbrain progenitors toward neuronal fate and dopaminergic phenotype [14].
• Furthermore, in several organ systems, TGF beta 3 transcripts are expressed during periods of active morphogenesis suggesting that the protein may be an important factor for the growth and differentiation of many embryonic tissues [15].
• Developing alveolar tissue and its associated ducts displayed striking TGF-beta 3 immunoreactivity which was greatly reduced during lactation [16].

Anatomical context of Tgfb3

• RESULTS: TGF-beta2 was detected in endocrine cells, whereas TGF-beta3 was predominantly found in goblet cells [7].
• For example, specific localization of TGF beta 1 was observed in the lens fibers of the eye (ectoderm), TGF beta 2 in the cortex of the adrenal gland (mesoderm), and TGF beta 3 in the cochlear epithelium of the inner ear (endoderm) [8].
• Our studies revealed overlapping expression patterns of TGF-beta 1, TGF-beta 2 and TGF-beta 3 within the epithelium of the actively-growing mammary end buds during branching morphogenesis, as well as within the epithelium of growth-quiescent ducts [16].
• However, TGF-beta 3 was the only isoform detected in myoepithelial progenitor cells (cap cells) of the growing end buds and myoepithelial cells of the mature ducts [16].
• Interestingly, addition of TGF-beta3 to the culture medium which caused fusion between the -/- palatal shelves also induced the appearance of these filopodia on their MEE surfaces [17].

Associations of Tgfb3 with chemical compounds

• Odontoblast-like cells obtained in the presence of IGF-1 combined with heparin did not express TGF beta 1 transcripts and expressed weakly TGF beta 3 transcripts [18].
• We analyzed the expression pattern of transforming growth factor-beta isoforms (TGF-beta1, TGF-beta2 and TGF-beta3) in the developing brain of embryos derived from the normal and diabetic mice exposed to cyclophosphamide (CP), a cytotoxic teratogen [19].
• The increases in mRNA steady-state levels for TGF-beta 2 and TGF-beta 3, as for TGF-beta 1, were rapid and transient in nature, again arguing for direct mediation by RA [20].
• Exposure of early neural plate stage embryos to retinoic acid caused reduced expression of TGF beta 1 and TGF beta 2 proteins but had no effect on TGF beta 3 [21].
• In comparison, neither an injection of E2 nor one of P4 exerted significant effects on TGF beta 3 mRNA levels.(ABSTRACT TRUNCATED AT 400 WORDS)[22]

Regulatory relationships of Tgfb3

• Stimulation of TtT/GF cells with either TGF-beta1 or TGF-beta3 induced a rapid translocation of Smad2 into the cell nuclei [23].
• Antisense oligonucleotides to CRABP-I partially inhibited the RA-induced TGF-beta 3, RAR-beta, and tenascin mRNA expression [24].
• TGF beta 2 is widely expressed at all stages investigated while TGF beta 3 is not expressed strongly in any tissue at the stages examined [21].
• TGF-beta3 regulates anchoring junction dynamics in the seminiferous epithelium of the rat testis via the Ras/ERK signaling pathway: An in vivo study [25].
• In tandem, TGF-beta 3 induced the expression and activity of MMP-9 [5].

Other interactions of Tgfb3

• GDF5, TGF-beta2, and TGF-beta3 showed maximal expression on day 7, when type II collagen expression peaked during cartilage formation [26].
• Coimmunoprecipitations demonstrated interaction between P311 and TGF-beta1 and 2, but not TGF-beta3 [27].
• In TGF-beta3 null mice, Pax9 expression was much reduced in the palatal medial edge at the critical time of palatal fusion (E14.5-E15.5) [1].
• TGF-beta2 null mice exhibit a broad range of developmental defects, including cardiac, lung, craniofacial, limb, eye, ear and urogenital defects, whereas TGF-beta3 gene ablation results exclusively in defective palatogenesis and delayed pulmonary development [28].
• Targeted disruption of both TGF-beta2 and TGF-beta3 genes results in perinatal lethality [28].

Analytical, diagnostic and therapeutic context of Tgfb3

• Whole mount in situ hybridization was conducted with use of Pax9 and Shh riboprobes for TGF-beta3 null, heterozygous and wild type mice at E12.5-E16 [1].
• METHODS: Intestinal localization of TGF-beta2 and TGF-beta3 isoforms and antiapoptotic molecules Bcl-xL and Bcl-2 was examined immunocytochemically and by Western blot analysis [7].
• Based on this pharmacokinetic data, we next administered neutralizing antibodies to TGF-beta1 and -beta2 or exogenous TGF-beta3 peptide by local application and intraperitoneal injection at various times before and after surgery [29].
• The remaining activity in CM correlates with high expression of TGF-beta 3 by Northern blot analysis in these cells [30].
• Prevention of mature TGF-beta 3 activity during a specific time window of development in palate organ cultures, either by antisense oligodeoxynucleotides or neutralizing antibody, resulted in failure of palate fusion [31].

References