Increased gastroduodenal concentrations of transforming growth factor alpha in adaptation to aspirin in monkeys and rats

Romano, Marco; Lesch, Charles; Meise, KS; Veljača, Marija; Sánchez, Benigno; Kraus, E R; Boland, C. Richard; Guglietta, Antonio; Rj, Coffey

doi:10.1053/gast.1996.v110.pm8613050

Cited by 22 publications

(16 citation statements)

References 15 publications

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“…Considering this, together with our finding that apoptosis is reduced (Alderman et al, 2000) and TGF-␣ is increased in adapted stomach (Doljanin et al, 1996;Romano et al, 1996), it is plausible that increased expression of TGF-␣ during adaptation might be an upstream signal that contributes to increased numbers of gastric mucosal ECL cells, in turn enhancing mucosal levels of RegI.…”

Section: Discussionmentioning

confidence: 72%

“…This is in keeping with the lesser degree of injury caused by the aspirin dose used in this study compared with the other more extensive injury models. Similarly, measurable increases in TGF-␣ and epidermal growth factor also occur in adapted stomachs only after multiple doses of aspirin and not after a single injurious dose (Doljanin et al, 1996;Konturek et al, 1994aKonturek et al, , 1998aRomano et al, 1996). It is possible that the increments in mucosal RegI (and indeed TGF-␣ and epidermal growth factor) that occur as a result of each adapting dose finally culminate as an "effective" increase only after several episodes of daily injury-this would help to explain the lag time of several days required for the onset of adaptation St John et al, 1973;Wallace et al, 1995).…”

Section: Alderman Et Almentioning

confidence: 98%

“…Several studies in both humans and experimental animals using histologic assessments and incorporation of 3 [H]thymidine and bromodeoxyuridine conclude that enhanced proliferation likely contributes to the mechanism of reduced injury that is characteristic of gastric mucosal adaptation (Baumgartner et al, 1986;Eastwood and Quimby, 1982;Konturek et al, 1994a;Lev et al, 1972;Levi et al, 1992;Romano et al, 1996;Shorrock et al, 1990). A role A, mRNA expression of regenerating protein (RegI) and its receptor (Regr) in the gastric mucosa of control, single-dose, and adapted rats 4 hours after the last dose of vehicle or aspirin.…”

Section: Alderman Et Almentioning

confidence: 99%

“…Adaptation is strongly associated with increased gastric epithelial cell proliferation (Baumgartner et al, 1986;Eastwood and Quimby, 1982;Konturek et al, 1994b;Lev et al, 1972;Levi et al, 1992;Shorrock et al, 1990;Yeomans et al, 1973) and increased mucosal expression of transforming growth factor-alpha (TGF-␣) (Doljanin et al, 1996;Konturek et al, 1998b;Romano et al, 1996;Stachura et al, 1996).…”

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confidence: 99%

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Insights into the Mechanisms of Gastric Adaptation to Aspirin-Induced Injury: A Role for Regenerating Protein but Not Trefoil Peptides

Alderman

Ulaganathan

Judd

et al. 2003

Laboratory Investigation

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SUMMARY:The phenomenon of reduced gastric mucosal injury despite repeated doses of a damaging agent is termed adaptation. Adaptation to nonsteroidal anti-inflammatory drug-induced injury has been clearly demonstrated in both humans and experimental animals; however, the precise mechanisms remain unclear. We hypothesized that mediators of adaptation might be the regenerating protein (RegI) and the trefoil peptides TFF1 and TFF2, because these proteins play pivotal roles in gastric mucosal protection and repair. The gene expression and the protein levels of these proteins were measured and compared in normal, aspirin-injured, and aspirin-adapted rat stomachs. TFF gene and protein expression levels were similar in all three groups, whereas RegI gene expression and protein levels in adapted stomach were increased. A time course analysis of RegI expression during the onset and offset of adaptation showed that mucosal RegI increased during the development of adaptation, was maintained during subsequent aspirin dosing, and returned to baseline levels once dosing had ceased and adaptation was lost-indicative of a causal role in the adaptation process. Colocalization of increased RegI with gastric epithelial areas showing increased proliferation also suggests that RegI may be an important mediator of the resolution of mucosal injury that is characteristic of gastric adaptation to aspirin. (Lab Invest 2003, 83:1415-1425.

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Section: Discussionmentioning

confidence: 72%

Section: Alderman Et Almentioning

confidence: 98%

Section: Alderman Et Almentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Insights into the Mechanisms of Gastric Adaptation to Aspirin-Induced Injury: A Role for Regenerating Protein but Not Trefoil Peptides

Alderman

Ulaganathan

Judd

et al. 2003

Laboratory Investigation

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“…Other changes that may be relevant to the mechanism of adaptation include the induction of growth factors such as transforming growth factor alpha (TGF-␣) [7] and Reg (a gene first noted to be upregulated in regenerating pancreas; Unpublished observations), both at a similar time to the onset of adaptation.…”

Section: Mechanism(s) Of Adaptationmentioning

confidence: 99%