HEPATOCYTE GROWTH-FACTOR INDUCES GASTRIC H+ K+-ATPASE EXPRESSION/

The processes regulating the development of the fetal gastrointestinal tract are largely unknown, but are likely dependent, in part, on pept ide growth factors. The purpose of this study was to determine the con tribution of hepatocyte growth factor (HGF) to the development of the fetal gastric epithelium, with particular reference to the parietal ce ll. Fifty-six fetal rabbits from 18 time-mated pregnant New Zealand Wh ite rabbit does were divided into four groups at Day 23 of gestation ( term is 31 days): (1) unoperated control littermates, (2) those preven ted from swallowing amniotic fluid by esophageal ligation (EL), (3) th ose with EL plus intragastric carrier infusion, and (4) those with EL plus intragastric HGF infusion. At Day 28 of gestation, fetal stomachs were harvested and analyzed for gastric weight, DNA content, and H+/K +-ATPase expression. In control fetuses, gastric weight was 470 +/- 30 mg, gastric DNA content was 741 +/- 59 mu g, and gastric H+/K+-ATPase expression was 25.4 +/- 2.7 mu g. EL resulted in a 45% decrease in ga stric weight (P = 0.001), a 34% decrease in DNA content (P = 0.04), an d a 43% decrease in H+/K+-ATPase expression (P = 0.007). These inhibit ory effects were not reversed by intragastric carrier infusion. Althou gh intragastric HGF infusion did not significantly restore gastric wei ght or gastric DNA content, it restored gastric H+/K+-ATPase expressio n to levels no different from those of unoperated controls (23.9 +/- 2 .8 mu g), but significantly greater than those of the EL or carrier in fusion groups (P = 0.01). These data suggest that HGF may be an import ant factor regulating the expression of H+/K+-ATPase and the developme nt of the fetal parietal cell. (C) 1995 Academic Press, Inc.