| The trefoil peptides are a small family of abundant polypeptide, secreted predominantly by mucus cells of the gut. This family have 3 members in mammalian: TFF1 or PS2, a stomach peptide; TFF2 or spasmolytic polypeptide, a distal stomach and pancreatic peptide; and TFF3 or intestinal trefoil factor found mainly in the intestine and colon. Each peptide have homology to another peptide in cysteine-rich regions of 38 or 39 amino acids known as trefoil motifs in which the component cysteine residues form disulphide bonds in an invariable 1-5,2-4,3-6 design, resulting in a compact triple-loop structure. This structural motif is extremely stable, and the basis for the extraordinary resistance to acid hydrolysis and proteolysis. It is now well established that trefoil peptides have cytoprotective functions in protecting the gastrointestinal tract against ongoing damage from agents as diverse as ethanol, non-steroidal anti-inflammatory drugs and restraint stress. The mechanism for this action is unclear. The pronounced and protracted increase in trefoil peptide expression in the inflamed and ulcerated stomach, intestinal and colon, implicates peptides in reparative processes of the injury gut. The administration of recombinant trefoil peptides can augment the healing process of ulcer. There were many evidences that trefoil peptides take part in the early phase of epithelial repair known as restitution (marked by increased cell migration), and in protracted phase of glandular renewal (marked by proliferation, differentiation and migration). The EGF-family of peptides includes several growth factors, which share both common sequence homology and affinity for the same EGF receptor. TGF-α is a 50 amino acid polypeptide produced in normal gastric mucosa. 35% of TGF-α sequence is homology to that of EGF that elicits its responses similar to EGF. TGF-α promotes cell proliferation, inhibites gastric acid secretion and exhibits gastroprotective activity against acute damage induced by topical irritants or stress. In addition, an increased TGF-α mRNA expression has been detected during healing of chronic experimental ulcers and acute damage of gastric mucosa in rats, suggesting its important role in gastric mucosal repair. Biological significance of TGF-α in mucosal repair was recently supported by the observation that the TGF-α knockout mice, lacking TGF-α gene, are more susceptible than normal rats to mucosal injury induced by various damaging agents.Previous studies showed that COX-2 is an inducible enzyme. Recently studies suggested that COX-2 is a constitutive enzyme expressed in GI tract also, even plays more important role than COX-1 for mucosal integrity. Gut epithelial COX-2 is rapidly induced by inflammatory stimuli, interleukin and transforming growth factor alpha. Suppression of COX-2 resulted in exacerbation of inflammation-associated colonic injury, and impaired the healing of gastric ulcer. Stress is known to induce gastric ulceration, but the mechanism of the early epithelial repair of stress-induced gastric lesion and the expression of PS-2, ITF has been little studied. Gastric mucosa can enhanced resistance to injury after exposure to repeated insults of noxious agents such as aspirin (ASA), alcohol, stress or HP-related gastrotoxins. This phenomenon is called gastric adaptation. But the mechanism of this phenomenon has not been fully explained. Recently, it has been postulated that the gastric adaptation involves enhancement of gastric blood flow and increased mucosal cell proliferation mediated by some growth factors such as epidermal growth factor (EGF) or transforming growth factor alpha (TGF-α). The fact that the adaptation to stress is associated with increased cell proliferation let us to hypothesize that this process might be mediated by TGF-α, PS-2 and ITF. The aim of the present study was to determine the expression of the PS-2, ITF in the early phase of epithelial repair of stress-induced gastric lesion and the expression of PS-2, ITF and transforming growth factor alpha (...
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