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Nitsche, H; Ramamoorthy, S; Sareban, M; Pausawasdi, N; Todisco, A.
Functional role of bone morphogenetic protein-4 in isolated canine parietal cells.
Am J Physiol Gastrointest Liver Physiol. 2007; 293(3): G607-G614. [OPEN ACCESS]
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Authors Med Uni Graz:
Jasser-Nitsche Hildegard
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Abstract:
Bone morphogenetic protein (BMP)-4 is an important regulator of cellular growth and differentiation. Expression of BMP-4 has been documented in the gastric mucosa. We reported that incubation of canine parietal cells with EGF for 72 h induced both parietal cell morphological transformation and inhibition of H(+)/K(+)-ATPase gene expression through MAPK-dependent mechanisms. We explored the role of BMP-4 in parietal cell maturation and differentiation. Moreover, we investigated if BMP-4 modulates the actions of EGF in parietal cells. H(+)/K(+)-ATPase gene expression was examined by Northern blots and quantitative RT-PCR. Acid production was assessed by measuring the uptake of [(14)C]aminopyrine. Parietal cell apoptosis was quantitated by Western blots with anti-cleaved caspase 3 antibodies and by counting the numbers of fragmented, propidium iodide-stained nuclei. MAPK activation and Smad1 phosphorylation were measured by Western blots with anti-phospho-MAPK and anti-phospho-Smad1 antibodies. Parietal cell morphology was examined by immunohistochemical staining of cells with anti-H(+)/K(+)-ATPase alpha-subunit antibodies. BMP-4 stimulated Smad1 phosphorylation and induced H(+)/K(+)-ATPase gene expression. BMP-4 attenuated EGF-mediated inhibition of H(+)/K(+)-ATPase gene expression and blocked EGF induction of both parietal cell morphological transformation and MAPK activation. Incubation of cells with BMP-4 enhanced histamine-stimulated [(14)C]aminopyrine uptake. BMP-4 had no effect on parietal cell apoptosis, whereas TGF-beta stimulated caspase-3 activation and nuclear fragmentation. In conclusion, BMP-4 promotes the induction and maintenance of a differentiated parietal cell phenotype. These findings may provide new clues for a better understanding of the mechanisms that regulate gastric epithelial cell growth and differentiation.
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Aminopyrine - metabolism
Animals - metabolism
Apoptosis - metabolism
Bone Morphogenetic Proteins - metabolism
Cell Differentiation - metabolism
Cell Shape - metabolism
Cells, Cultured - metabolism
Dogs - metabolism
Epidermal Growth Factor - metabolism
Gastric Acid - secretion
Gastric Fundus - cytology
Gene Expression Regulation, Enzymologic - cytology
H(+)-K(+)-Exchanging ATPase - genetics
Histamine - metabolism
Mitogen-Activated Protein Kinase 1 - metabolism
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Phenotype - enzymology
Phosphorylation - enzymology
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