Dedifferentiation and proliferation of retinal pigment epithelial (RPE) cells are characteristics
of retinal diseases. Dedifferentiation is likely associated with changes of inwardly rectifying
potassium (Kir) channels. The roles of Kir4.2 channels in viability, and proliferation of cultured RPE
cells were investigated. Gene expression levels were determined using qRT-PCR. RPE cells expressed
Kir2.1, 2.2, 2.4, 3.2, 4.1, 4.2, 6.1, and 7.1 mRNA. Kir4.2 protein was verified by immunocytochemistry
and Western blotting. Kir4.2 mRNA in cultured cells was upregulated by hypoxia (hypoxia mimetic
CoCl2 or 0.2% O2) and extracellular hyperosmolarity (addition of high NaCl or sucrose). Kir4.2
mRNA was suppressed by vascular endothelial growth factor (VEGF), blood serum, and thrombin
whereas platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and transforming
growth factor-1 (TGF-1) increased it. Hyperosmotic Kir4.2 gene expression was mediated
by TGF-1 receptor signaling while hypoxic gene transcription was dependent on PDGF receptor
signaling. 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 and
proliferation under control and hyperosmotic conditions. Kir4.2 channels play functional roles in
maintaining the viability and proliferation of RPE cells. Downregulation of Kir4.2 by VEGF, via
activation of VEGF receptor-2 and induction of blood-retinal barrier breakdown, may contribute to
decreased viability of RPE cells under pathological conditions.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:87685 |
| Date | 26 October 2023 |
| Creators | Beer, Marie-Christian, Kuhrt, Heidrun, Kohen, Leon, Wiedemann, Peter, Bringmann, Andreas, Hollborn, Margrit |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 848 |
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