Disease relevance of TGFA

• Epithelial wound healing enhanced by transforming growth factor-alpha and vaccinia growth factor [1].
• Oral transforming growth factor-alpha enhances jejunal mucosal recovery and electrical resistance in piglet rotavirus enteritis [2].
• Since TGF alpha is produced by hepatocytes during liver regeneration and by macrophages during endotoxin stimulation, it may have an autocrine/paracrine effect on hepatic carbohydrate metabolism in these states, and may account for the low hepatic glycogen levels during liver regeneration and the impaired glucose tolerance associated with sepsis [3].

High impact information on TGFA

• Transforming growth factor-alpha (TGF-alpha) and vaccinia growth factor (VGF) have substantial sequence homology with EGF, and all appear to bind to the same receptor protein [1].
• Regenerated epithelium from burns treated with TGF-alpha or VGF appeared normal histologically [1].
• When administered prior to the secretagogue, TGF-alpha prevented the histamine-induced increase in the rate of acid secretion [4].
• Transforming growth factor alpha inhibits secretion of gastric acid [4].
• Expression of the genes for TGF alpha, EGF and the EGF receptor during early pig development [5].

Biological context of TGFA

• Nucleotide sequence analysis predicts a 160-residue transmembrane polypeptide that differs from the rat, mouse and human TGF alpha precursors at 14, 15 and six sites respectively [6].
• Molecular cloning and tissue distribution of pig transforming growth factor alpha [6].
• Whether TGF-alpha or VGF can affect epidermal wound healing in vivo is not known [1].
• Hydrolysis of transforming growth factor-alpha by cell-surface peptidases in vitro [7].
• Cellular distribution of EGF, TGFalpha and their receptor during postnatal development and spermatogenesis of the boar testis [8].

Anatomical context of TGFA

• Interestingly, TGF alpha mRNA was expressed by the developing blastocyst only at days 8, 10 and 12 of pregnancy, with the highest levels apparent at day 10 [5].
• In the unfertilised pig oocyte, maternal transcripts for EGF, but not for TGF alpha or the EGF-R, were detected [5].
• Extracts from weanling pig liver were found to act synergistically with growth factors such as hepatocyte growth factor and transforming growth factor-alpha to stimulate hepatocyte growth in serum-free cultures [9].
• In parallel, we measured the receptor binding affinities for epidermal growth factor-urogastrone (EGF-URO) and transforming growth factor-alpha (TGF-alpha) in cultured smooth muscle (GCM) and epithelial (GPC) cells derived from guinea pig intestine [10].
• The results of these studies demonstrated that the basal transport properties of endometrial epithelial cells are differentially regulated by EGF, TGFalpha, and insulin [11].

Associations of TGFA with chemical compounds

• L-glutamine and transforming growth factor-alpha enhance recovery of monoacylglycerol acyltransferase and diacylglycerol acyltransferase activity in porcine postischemic ileum [12].
• Loops were subjected to 2-h occlusion of local mesenteric arteries, followed by 6 or 72 h of recovery in the presence of luminal glucose (control), Gln, or TGF-alpha [12].
• The inhibition by genistein and tyrphostin of EGF-URO and TGF-alpha mediated contraction was rapid (beginning within minutes) and was reversible upon washing the preparations free from the enzyme inhibitors [13].
• During the recovery, the tissue was exposed bilaterally either to modulators of cytoskeleton (cytochalasin B/lysophosphatidic acid) or of tyrosine receptor mediated signalling (genistein/epidermal growth factor + transforming growth factor-alpha) [14].

Regulatory relationships of TGFA

• These data show that TGF-alpha inhibits gastric acid secretion in a manner similar to EGF and that the two growth factors share at least one physiological action unrelated to their mitogenic properties [4].
• EGF and TGF alpha (5 ng/mL each) enhanced TGF beta 1 mRNA about threefold within 4 and 8 hours [15].

Other interactions of TGFA

• At 72 h, MGAT and DGAT recovery in Gln plus TGF-alpha-treated loops was significantly greater than their corresponding 6-h peak damage levels (p < 0.05) [12].
• Low levels of both TGF-alpha and VGF (0.1 microgram per milliliter) appeared to be more effective than EGF in stimulating epidermal regeneration [1].
• Modulation of transforming growth factor-beta 1 stimulated elastin and collagen production and proliferation in porcine vascular smooth muscle cells and skin fibroblasts by basic fibroblast growth factor, transforming growth factor-alpha, and insulin-like growth factor-I [16].
• In the smooth muscle cell, both bFGF and TGF-alpha were potent antagonists of TGF-beta 1-mediated matrix production, whereas IGF-1 was only weakly additive with respect to elastin production [16].

Analytical, diagnostic and therapeutic context of TGFA

• Therefore, an amplified DNA fragment encoding the pig TGF alpha precursor was cloned by reverse transcription-PCR (RT-PCR) using RNA isolated from normal skin tissue as the template [6].
• The present studies show that topical administration of TGF-alpha or VGF in antibiotic cream to partial thickness burns (second degree) accelerated epidermal regeneration in comparison with untreated or vehicle-treated burns [1].
• Three of such genes were shown by sequence analysis to be the porcine transforming growth factor-alpha, the porcine transforming growth factor-beta-binding protein II and a porcine astral natriuretic factor receptor-like transcript [17].
• Detection of an EGF/TGF-alpha receptor was also confirmed by Western blotting [18].
• Immunofluorescence microscopy of GMEC cultures for EGF/TGF-alpha receptors showed increased fluorescence at the leading edges and around the perimeter of cells [18].

References