Downregulation of miR-503 in Activated Kidney Fibroblasts Disinhibits KCNN4 in an in Vitro Model of Kidney Fibrosis
| Autor: | Christoph Mann, Brajesh Pratap Kaistha, Michael Kacik, Thorsten Stiewe, Joachim Hoyer |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Kidney & Blood Pressure Research, Vol 44, Iss 1, Pp 113-122 (2019) |
| Druh dokumentu: | article |
| ISSN: | 1420-4096 1423-0143 |
| DOI: | 10.1159/000498875 |
| Popis: | Background/Aims: Activated fibroblasts are key controllers of extracellular matrix turnover in kidney fibrosis, the pathophysiological end stage of chronic kidney disease. The proliferation of activated fibroblasts depends on the expression of the calcium-dependent potassium channel KCNN4. Expression of this ion channel is upregulated in fibrotic kidneys. Genetic and pharmacological blockade of KCNN4 inhibits fibrosis in vitro and in vivo. Methods: We studied the regulation of KCNN4 and possible involvement of miRNAs in an in-vitro fibrosis model using murine kidney fibroblasts. We tested fibroblast proliferation, channel function, channel expression and expression regulation after FGF-2 stimulation. Results: Proliferation was significantly increased by FGF-2, channel current and expression were almost doubled (+ 91% and +125%, respectively). MiRNA microarray identified upregulation of miRNA-503, which targets RAF1 and thereby controls KCNN4-expression via disinhibition of the Ras/Raf/MEK/ ERK-cascade. Conclusion: This data show a) a profound upregulation of KCNN4 in stimulated fibroblast and b) identifies miR-503 as a regulator of KCNN4 expression. |
| Databáze: | Directory of Open Access Journals |
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