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Medientyp:
E-Artikel
Titel:
Kir4.2 Potassium Channels in Retinal Pigment Epithelial Cells In Vitro
:
Contribution to Cell Viability and Proliferation, and Down-Regulation by Vascular Endothelial Growth Factor
Beteiligte:
Beer, Marie-Christian
[VerfasserIn];
Kuhrt, Heidrun
[VerfasserIn];
Kohen, Leon
[VerfasserIn];
Wiedemann, Peter
[VerfasserIn];
Bringmann, Andreas
[VerfasserIn];
Hollborn, Margrit
[VerfasserIn]
Beschreibung:
Dedifferentiation and proliferation of retinal pigment epithelial (RPE) cells are characteristicsof retinal diseases. Dedifferentiation is likely associated with changes of inwardly rectifyingpotassium (Kir) channels. The roles of Kir4.2 channels in viability, and proliferation of cultured RPEcells were investigated. Gene expression levels were determined using qRT-PCR. RPE cells expressedKir2.1, 2.2, 2.4, 3.2, 4.1, 4.2, 6.1, and 7.1 mRNA. Kir4.2 protein was verified by immunocytochemistryand Western blotting. Kir4.2 mRNA in cultured cells was upregulated by hypoxia (hypoxia mimeticCoCl2 or 0.2% O2) and extracellular hyperosmolarity (addition of high NaCl or sucrose). Kir4.2mRNA was suppressed by vascular endothelial growth factor (VEGF), blood serum, and thrombinwhereas platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and transforminggrowth factor-1 (TGF-1) increased it. Hyperosmotic Kir4.2 gene expression was mediatedby TGF-1 receptor signaling while hypoxic gene transcription was dependent on PDGF receptorsignaling. VEGF receptor-2 blockade increased Kir4.2 mRNA level under control, hyperosmotic,and hypoxic conditions. SiRNA-mediated knockdown of Kir4.2 decreased the cell viability andproliferation under control and hyperosmotic conditions. Kir4.2 channels play functional roles inmaintaining the viability and proliferation of RPE cells. Downregulation of Kir4.2 by VEGF, viaactivation of VEGF receptor-2 and induction of blood-retinal barrier breakdown, may contribute todecreased viability of RPE cells under pathological conditions.