Regulation of Parietal Cell Homeostasis by Bone Morphogenetic Protein Signaling.

ABSTRACT:

Background and aims

Loss of bone morphogenetic protein (BMP) signaling in the stomach, achieved by transgenic expression of the BMP inhibitor noggin (H ⁺ /K ⁺ -Nog mice), causes parietal cell (PC) loss, spasmolytic polypeptide-expressing metaplasia, a marker of preneoplasia, and activation of cell proliferation. We examined if specific inhibition of BMP signaling in PCs leads to aberrations in epithelial homeostasis.

Methods

Mice with floxed alleles of BMP receptor 1a (Bmpr1a ^flox/flox mice) were crossed to H ⁺ /K ⁺ -Cre mice to generate H ⁺ /K ⁺ -Cre;Bmpr1a ^flox/flox mice. Morphology of the mucosa was analyzed by hematoxylin and eosin staining. Distribution of H⁺/K⁺-ATPase-, IF-, and Ki-67-positive cells was analyzed by immunostaining. Expression of pit and neck cell mucins was determined by staining with the lectins Ulex Europaeus Agglutinin 1 and Griffonia (Bandeiraea) simplicifolia lectin II, 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.

Results

Six-month-old H ⁺ /K ⁺ -Cre;Bmpr1a ^flox/flox mice exhibited increased epithelial cell proliferation, presence of transitional cells showing colocalization of IF with both Griffonia (Bandeiraea) simplicifolia lectin II-binding mucins and the H⁺/K⁺-ATPase, and expansion of Ulex Europaeus Agglutinin 1-positive cells. PC transcripts from Nog-expressing mice demonstrated induction of markers of Spasmolytic Polypeptide-Expressing Metaplasia.

Conclusion

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

SUBMITTER: Takabayashi H 

PROVIDER: S-EPMC11307507 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature