Disease relevance of Tgfa

• Transforming growth factor-alpha attenuates N-methyl-D-aspartic acid toxicity in cortical cultures by preventing protein synthesis inhibition through an Erk1/2-dependent mechanism [1].
• Transforming growth factor-alpha (TGF-alpha), a ligand of the epidermal growth factor receptor, reduces the infarct size after focal cerebral ischemia in rat, but the molecular basis underlying the protection is unknown [1].
• Here we report that transforming growth factor-alpha (TGF-alpha), an EGFR ligand that is frequently secreted by colorectal cancer cells, strongly inhibits anoikis of the non-malignant rat intestinal epithelial cell lines, IEC-18 and RIE-1 [2].
• Stimulation of bone resorption in vitro by synthetic transforming growth factor-alpha [3].
• Blockade of TGF-alpha action in the median eminence, a site of glial-LHRH nerve terminal association, delayed puberty [4].
• To examine correlations between the increased levels of TGFalpha in experimental knee osteoarthritis (OA) with the levels of TGFalpha in humans with knee OA, a microarray analysis of mRNA from 13 normal and 12 late-stage OA cartilage samples was performed [5].

Psychiatry related information on Tgfa

• These findings reveal a new population of striatal cells, calretinin neurons, that are relatively resistant to quinolinic acid toxicity and that neurotrophin-4/5 and transforming growth factor-alpha partially protect against the phenotypic degeneration of striatal cell populations in an in vivo animal model of Huntington's disease [6].

High impact information on Tgfa

• Integral membrane glycoprotein properties of the prohormone pro-transforming growth factor-alpha [7].
• In glial cells it may interact with epidermal growth factor (EGF) receptors to further enhance TGF alpha synthesis and to, perhaps, stimulate eicosanoid formation [8].
• Evidence is beginning to emerge suggesting that development of the reproductive hypothalamus is affected by insulin-like growth factor 1 secreted by peripheral tissues, and transforming growth factor alpha (TGF alpha) produced locally [8].
• In the rat hypothalamus, TGF alpha appears to be synthesized in both neurons and glial cells [8].
• Moreover, oxidative stress, TGF alpha and collagen type I markedly stimulated stellate cell entry into S-phase, NFkB activity, and c-myb expression, which were prevented by antioxidants. c-myb antisense oligonucleotide blocked the activation and proliferation of stellate cells induced by TGF alpha [9].

Chemical compound and disease context of Tgfa

• To develop novel strategies that might inhibit or prevent restenosis, we previously used a chimeric toxin composed of transforming growth factor-alpha (which targets the epidermal growth factor receptor) and mutated Pseudomonas exotoxin to preferentially recognize and kill rapidly proliferating, versus quiescent, vascular SMCs [10].
• The induction of adenocarcinomas in the glandular stomach of the adult male Wistar rat by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was used as a model to study the expression of the growth promoting peptide, transforming growth factor alpha (TGF alpha), during experimental gastric carcinogenesis [11].
• CONCLUSION: These results support a significant role for the EGF/TGF-alpha/EGFR axis in the development of PKD in the Han:SPRD rat and the therapeutic potential of EGFR tyrosine kinase inhibition in ADPKD [12].
• It is concluded that putative preneoplastic acinar cell lesions induced in rat pancreas by azaserine may develop into acinar adenocarcinomas independently of TGF-alpha and EGF [13].
• Conversely, prevention of the increases in both TGF-alpha and EGFR paralleled the efficacy of either P restriction or high-Ca intake in ameliorating uremia-induced parathyroid hyperplasia [14].

Biological context of Tgfa

• TGF-alpha induced a prompt and sustained phosphorylation of Erk1/2 and prevented the loss of Akt-P induced by NMDA 3 h after exposure [1].
• We found that 100 ng/ml TGF-alpha attenuated neuronal cell death induced by a 30-min exposure to 35 microM N-methyl-D-aspartic acid (NMDA) (as it reduced lactate dehydrogenase release, propidium iodide staining, and caspase-3 activation) and decreased the elevation of intracellular Ca2+ elicited by NMDA [1].
• Here we studied whether TGF-alpha can rescue neurons from excitotoxicity in vitro and how it affects calcium homeostasis, protein synthesis, and the associated Akt and extracellular signal-regulated kinase 1/2 (Erk1/2) intracellular signaling pathways in mixed neuron-glia cortical cultures [1].
• Conclusion: The increased expression of TGF-alpha and its receptor in the obstructed kidney might be related to a cell-survival function in the affected cells possibly by protecting them from entering apoptosis [15].
• Moreover, little is known about possible interactions of TGF-alpha and laminin and fibronectin in basement membranes during estrous cycles in relation to follicle development [16].

Anatomical context of Tgfa

• Results: Levels of EGF mRNA remained stable in rat corneas after ablation (68 +/- 12 copies/cell, mean +/- SD), whereas levels of TGF-alpha mRNA progressively increased sixfold to a maximum at day 42 (300 copies/cell) then slightly decreased on day 91 [17].
• Varying amounts of TGF-alpha were found in granulosa cells and interstitial thecal cells which form follicles [16].
• It was found that TGF-alpha was predominantly localised in nuclei of oocytes [16].
• Increased TGF-alpha and EGF Receptor mRNA Expression in Response to Neonatal Unilateral Partial Ureter Obstruction in Rats [15].
• A novel mechanism for mitogenic signaling via pro-transforming growth factor alpha within hepatocyte nuclei [18].

Associations of Tgfa with chemical compounds

• (3) The frequency of hepatocytes coexpressing pro-TGF-alpha and DNA synthesis was increased by the hepatomitogens CPA or prostaglandin E(2) and was decreased by the growth inhibitor TGF-beta1 [18].
• In rat follicles cultured for 2 and 4 days, FSH stimulated estradiol production, TGFalpha secretion, XIAP expression, and follicular growth [19].
• Intrafollicular injection of a neutralizing anti-TGFalpha antibody (50-200 ng/ml; immunoglobulin G as control) or addition of estradiol-antagonist ICI 182780 (0.5-100 nM) to the culture media suppressed FSH-induced XIAP expression and follicular growth [19].
• Treatment with TGFalpha or EGF for 24h resulted in significant increase in androgen production in ILC [20].
• Furthermore, despite an increase in cPLA(2) including its phosphorylated form (phosphoserine), -induced arachidonic acid liberation was impaired in the TGF-alpha/IL-1beta-stimulated cells, in which p11, a putative cPLA(2) inhibitory molecule, was also increased and co-immunoprecipitated with cPLA(2) [21].

Physical interactions of Tgfa

• Scatchard analyses revealed that EGF receptors bound EGF with 4- to 8-fold higher affinity than TGF-alpha [22].
• Our results suggest that the TGF-alpha-induced stimulation of DNA binding activity of AP-1 in the gastric mucosa of aged rats is primarily through a signaling pathway involving MEKs and ERKs, whereas Src kinase pathways play a minor role [23].
• Transforming growth factor-alpha binds to the epidermal growth factor receptor in gastric mucosa [24].
• The glucose response element of the TGF alpha gene maps to a 130-base-pair segment that includes three potential binding sites for the transcription factor Sp1 [25].

Enzymatic interactions of Tgfa

• We conclude that MAPK is tyrosine phosphorylated in response to TGF-alpha stimulation of IEC-6 cells [26].

Regulatory relationships of Tgfa

• Transforming growth factor-alpha prevents detachment-induced inhibition of c-Src kinase activity, Bcl-XL down-regulation, and apoptosis of intestinal epithelial cells [2].
• In concurrence with these findings, PB down-regulated expression of the HGF receptor (c-met) and suppressed production of the autocrine growth factor transforming growth factor-alpha (TGF-alpha) [27].
• The transforming growth factor alpha-induced expression of cyclooxygenase-2 is followed by cell proliferation and development of tubular morphology of RGM1 gastric epithelial cells [28].
• TGF beta 1 inhibited TGF alpha-induced [3H]thymidine incorporation into peritubular cell DNA with cells from each developmental stage examined [29].
• IGF-I production by adult rat hepatocytes is stimulated by transforming growth factor-alpha and transforming growth factor-beta1 [30].

Other interactions of Tgfa

• The protective effect of TGF-alpha was completely prevented by PD 98059, an inhibitor of the Erk1/2 pathway [1].
• PD 98059 abrogated the TGF-alpha effect on eIF4E [1].
• Levels of mRNAs for EGF, TGF-alpha, TGF-beta isoforms 1, 2, and 3, and their receptors (EGF-R and TGFbeta-IIR) were measured by quantitative RT-PCR on days 0, 1.5, 7, 21, 42, and 91 after ablation [17].
• The extent of gastric mucosal lesions were evaluated grossly and histologically and expressions of COX-2, pS2,iNOS and TGFalpha were determined by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot [31].
• Distribution patterns of TGF-alpha, laminin and fibronectin and their relationship with folliculogenesis in rat ovary [16].

Analytical, diagnostic and therapeutic context of Tgfa

• The theca cells are the primary follicular source of FSH-induced TGFalpha, as indicated by in situ hybridization [19].
• High level copy number gains were not observed using CGH as well as semiquantitative PCR with Tgfa, Met and Hbb primers [32].
• Immunostaining revealed that cultures of hepatocytes, isolated from NNM-treated livers by collagenase perfusion, contained 1-2% GSTp-positive (GSTp(+)) and 9% TGFalpha(+) hepatocytes; 0.6% of the cells were GSTp(+)/TGFalpha(+) [33].
• Radioimmunoassay of gastric mucosal scrapings obtained 6 hours after gastric injury induced by 0.6 mol/L HCl showed a 2.1-fold increase in immunoreactive TGF-alpha but no increase in immunoreactive EGF [34].
• During liver regeneration after partial hepatectomy in rats, TGF-alpha mRNA increased; it reached a maximum (approximately 9-fold higher than normal) at the peak of DNA synthesis [35].

References