Regulation of Parietal Cell Homeostasis by Bone Morphogenetic Protein signaling

Open AccessPublished:October 13, 2022DOI:
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      Loss of BMP signaling in the stomach, achieved by transgenic expression of the BMP inhibitor noggin (H+/K+-Nog mice), causes parietal cells (PC) loss, SPEM, a marker of pre-neoplasia, and activation of cell proliferation.


      We examined if specific inhibition of BMP signaling in PCs leads to aberrations in epithelial homeostasis.


      Mice with floxed alleles of BMP receptor 1a (Bmpr1aflox/flox mice) were crossed to H+/K+-Cre mice to generate H+/K+-Cre;Bmpr1aflox/flox mice. Morphology of the mucosa was analyzed by H&E staining. Distribution of H+/K+-ATPase-, IF- and Ki-67+ve -positive cells was analyzed by immunostaining. Expression of pit and neck cell mucins was determined by staining with the lectins UEA1 and GSII, respectively. Isolation of PCs from control and Nog-expressing mice, was achieved by crossing H+/K+-Nog mice to Rosa26-tdTomato (Tom) mice to generate H+/K+-Nog;Rosa26-tdTom mice. H+/K+-Cre mice were then crossed to H+/K+-Nog;Rosa26-tdTom mice to generate H+/K+-Cre;H+/K+-Nog;Rosa26-tdTom mice. Tom-labeled PCs were purified by flow-cytometry. Changes in PC-transcripts were measured by RNA-Seq.


      Six-month-old H+/K+-Cre;Bmpr1aflox/flox mice exhibited increased epithelial cell proliferation, presence of transitional cells showing co-localization of IF with both GSII-binding mucins and the H+/K+-ATPase and expansion of UEA1+ve cells. PC-transcripts from Nog-expressing mice demonstrated induction of markers of SPEM.


      PC-specific loss of BMP signaling alters the homeostasis of the gastric epithelium leading to the development of metaplasia.