Role of the prostanoid FP receptor in action potential generation and phenotypic transformation of NRK fibroblasts
| Autor: | W.H.M.A. Almirza, E.J.J. van Zoelen, M.M. Dernison, Alexander P.R. Theuvenet, P.H.J. Peters |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
medicine.medical_specialty
Receptors Prostaglandin Retinoic acid Action Potentials Down-Regulation Prostaglandin Cell Count Tretinoin Dinoprost chemistry.chemical_compound Transforming Growth Factor beta Internal medicine medicine Animals Humans RNA Small Interfering Receptor Cell Line Transformed Cell Proliferation Gene knockdown biology Membrane Proteins Depolarization Cell Biology Transforming growth factor beta Fibroblasts Rats Cell biology Cell Transformation Neoplastic Phenotype Endocrinology chemistry Cyclooxygenase 2 Cell culture Enzyme Induction Cyclooxygenase 1 biology.protein hormones hormone substitutes and hormone antagonists Transforming growth factor |
| Zdroj: | Cellular Signalling, 20, 2022-2029 Cellular Signalling, 20, 11, pp. 2022-2029 |
| ISSN: | 0898-6568 |
| Popis: | By using an shRNA approach to knockdown the expression of the prostaglandin (PG)-F(2alpha) receptor (FP-R), the role of PGF(2alpha) in the process of phenotypic transformation of normal rat kidney (NRK) fibroblasts has been studied. Our data show that PGF(2alpha) up-regulates Cox-2 expression both at the mRNA and protein level, indicating that activation of FP-R in NRK fibroblasts induces a positive feedback loop in the production PGF(2alpha). Knockdown of FP-R expression fully impaired the ability of PGF(2alpha) to induce a calcium response and subsequent depolarization in NRK cells. However, these cells could still undergo phenotypic transformation when treated with a combination of EGF and retinoic acid, but in contrast to the wild-type cells, this process was not accompanied by a membrane depolarization to -20 mV. Knockdown of FP-R expression also impaired the spontaneous firing of calcium action potentials by density-arrested NRK cells. These data show that a membrane depolarization is not a prerequisite for the acquisition of a transformed phenotype. Furthermore, our data provide the first direct evidence that activity of PGF(2alpha) by putative pacemaker cells underlies the generation of calcium action potentials in NRK monolayers. |
| Databáze: | OpenAIRE |
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