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SHR Neuro Cancer Cardio Lipid Metab Microb
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.
Doi: 10.1152/ajpgi.00194.2006
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- Leading 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.
- Find related publications in this database (using NLM MeSH Indexing)
- 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
- Parietal Cells, Gastric - enzymology
- Phenotype - enzymology
- Phosphorylation - enzymology
- RNA, Messenger - metabolism
- Smad Proteins, Receptor-Regulated - metabolism
- Time Factors - metabolism
- Transforming Growth Factor beta - metabolism