G Protein-Coupled Receptor 37L1 Modulates Epigenetic Changes in Human Renal Proximal Tubule Cells
| Autor: | Ines Armando, Santiago Cuevas, Caini Fan, Megha Kumar, Zahra Izzi, Pedro A. Jose, Prasad R. Konkalmatt |
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| Rok vydání: | 2022 |
| Předmět: |
Sodium-Hydrogen Exchangers
Sodium-Hydrogen Exchanger 3 blood pressure DNMT1 epigenetics ETBR-LP2 G protein-coupled receptor GPCR GPR37L1 hypertension mass spectrometry NHE3 signaling pathway PI3/AKT/mTOR renal proximal tubule sodium transport Sodium Organic Chemistry General Medicine Catalysis Receptors G-Protein-Coupled Epigenesis Genetic Computer Science Applications Inorganic Chemistry Phosphatidylinositol 3-Kinases Humans Physical and Theoretical Chemistry Molecular Biology Spectroscopy |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 22; Pages: 14456 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms232214456 |
| Popis: | Renal luminal sodium transport is essential for physiological blood pressure control, and abnormalities in this process are strongly implicated in the pathogenesis of essential hypertension. Renal G protein-coupled receptors (GPCRs) are critical for the regulation of the reabsorption of essential nutrients, ions, and water from the glomerular filtrate. Recently, we showed that GPCR 37L1 (GPR37L1) is expressed on the apical membrane of renal proximal tubules (RPT) and regulates luminal sodium transport and blood pressure by modulating the function of the sodium proton exchanger 3 (NHE3). However, little is known about GPR37L1 intracellular signaling. Here, we show that GPR37L1 is localized to the nuclear membrane, in addition to the plasma membrane in human RPT cells. Furthermore, GPR37L1 signals via the PI3K/AKT/mTOR pathway to decrease the expression of DNA (cytosine-5)-methyltransferase 1 (DNMT1) and enhance NHE3 transcription. Overall, we demonstrate the direct role of a nuclear membrane GPCR in the regulation of renal sodium through epigenetic gene regulation. |
| Databáze: | OpenAIRE |
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