Almaca, Joana and Faria, Diana and Sousa, Marisa and Uliyakina, Inna and Conrad, Christian and Sirianant, Lalida and Clarke, Luka A. and Martins, Jose Paulo and Santos, Miguel and Heriche, Jean-Karim and Huber, Wolfgang and Schreiber, Rainer and Pepperkok, Rainer and Kunzelmann, Karl and Amaral, Margarida D. (2013) High-Content siRNA Screen Reveals Global ENaC Regulators and Potential Cystic Fibrosis Therapy Targets. CELL, 154 (6). pp. 1390-1400. ISSN 0092-8674, 1097-4172
Full text not available from this repository. (Request a copy)Abstract
Dysfunction of ENaC, the epithelial sodium channel that regulates salt and water reabsorption in epithelia, causes several human diseases, including cystic fibrosis (CF). To develop a global understanding of molecular regulators of ENaC traffic/function and to identify of candidate CF drug targets, we performed a large-scale screen combining high-content live-cell microscopy and siRNAs in human airway epithelial cells. Screening over 6,000 genes identified over 1,500 candidates, evenly divided between channel inhibitors and activators. Genes in the phosphatidylinositol pathway were enriched on the primary candidate list, and these, along with other ENaC activators, were examined further with secondary siRNA validation. Subsequent detailed investigation revealed ciliary neurotrophic factor receptor (CNTFR) as an ENaC modulator and showed that inhibition of (diacylglycerol kinase, iota) DGKi, a protein involved in PiP2 metabolism, downgrades ENaC activity, leading to normalization of both Na+ and fluid absorption in CF airways to non-CF levels in primary human lung cells from CF patients.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | EPITHELIAL SODIUM-CHANNEL; TRANSMEMBRANE CONDUCTANCE REGULATOR; NA+ CHANNEL; LUNG-DISEASE; ION CHANNELS; HUMAN GENOME; CFTR; TRANSPORT; AMILORIDE; CELLS; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 31 Mar 2020 12:58 |
| Last Modified: | 31 Mar 2020 12:58 |
| URI: | https://pred.uni-regensburg.de/id/eprint/16035 |
Actions (login required)
 |
View Item |
