A molecular profile of the mouse gastric parietal cell with and without exposure to Helicobacter pylori

The parietal cell (PC) plays an important role in normal gastric physiology and in common diseases of the stomach. Although the genes involved in acid secretion are well known, there is limited molecular information about oth er aspects of PC function. We have generated a comprehensive database of ge nes expressed preferentially in PCs relative to other gastric mucosal cell lineages. PCs were purified from FVB/N mouse stomachs by lectin panning. cR NA generated from PC-enriched (PC+) and PC-depleted (PC-) populations were used to query oligonucleotide-based microarrays. False-positive signals wer e filtered by using a new algorithm for noise reduction and selected result s independently audited by real-time quantitative reverse transcription (RT )-PCR. The annotated database of 240 genes reveals previously unappreciated aspects of cellular function, including factors that may mediate PC regula tion of gastric stem cell proliferation. PC+ and PC- expression profiles we re also prepared from germ-free mice 2 and 8 weeks after colonization with a clinical isolate of Helicobacter pylori (Hp)-the pathogen that produces a cid-peptic disease (gastritis, ulcers) in humans. Whereas PC+ gene expressi on was remarkably constant, the PC- fractions demonstrated a robust, evolvi ng host response, with increased expression of genes involved in cell motil ity/migration, extracellular matrix interactions, and IFN responses. The co nsistency of PC+ gene expression allowed identification of a cohort of 92 g enes enriched in PCs under all conditions studied. These genes provide a mo lecular profile that can be used to define this epithelial lineage under a variety of physiologic, pharmacologic, and pathologic stimuli.