Cabrita, Ines and Talbi, Khaoula and Kunzelmann, Karl and Schreiber, Rainer (2021) Loss of PKD1 and PKD2 share common effects on intracellular Ca2+ signaling. CELL CALCIUM, 97: 102413. ISSN 0143-4160, 1532-1991
Full text not available from this repository. (Request a copy)Abstract
In polycystic kidney disease (PKD) multiple bilateral renal cysts gradually enlarge causing a decline in renal function. Transepithelial chloride secretion through cystic fibrosis transmembrane conductance regulator (CFTR) and TMEM16A (anoctamin 1) drive cyst enlargement. We demonstrated recently that a loss of PKD1 increases expression and function of TMEM16A in murine kidneys and in mouse M1 collecting duct cells. The data demonstrated that TMEM16A contributes essentially to cyst growth by upregulating intracellular Ca2+ signaling. Enhanced expression of TMEM16A and Ca2+ signaling increased both cell proliferation and fluid secretion, which suggested inhibition of TMEM16A as a novel therapy in ADPKD. About 15 % of all ADPKD cases are caused by mutations in PKD2. To analyze the effects of loss of function of PKD2 on Ca2+ signaling, we knocked-down Pkd2 in mouse primary renal epithelial cells in the present study, using viral transfection of shRNA. Unlike in Pkd1-/- cells, knockdown of PKD2 lowered basal Ca2+ and augmented store-operated Ca2+ entry, which was both independent of TMEM16A. However, disease causing purinergic Ca2+ store release was enhanced, similar to that observed in Pkd1-/- renal epithelial cells. The present data suggest pharmacological inhibition of TMEM16A as a treatment in ADPKD caused by mutations in both PKD1 and PKD2.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHLORIDE SECRETION; CALCIUM; PROLIFERATION; DISEASE; ANO1; CONTRIBUTES; ANOCTAMINS; CHANNELS; GROWTH; Pkd1; Pkd2; ADPKD; Renal cysts; TMEM16A; Anoctamin 1; Ca2+ activated Cl- channel |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Aug 2022 12:05 |
| Last Modified: | 02 Aug 2022 12:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/46021 |
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