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.
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http://dx.doi.org/10.3390/ijms232214456 | DOI Listing |
Nephrol Dial Transplant
January 2025
Department of Nephrology, Kidney Transplantation and Dialysis, CHU Lille, University of Lille, Lille, France.
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Funct Integr Genomics
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Department of Emergency and Critical Care Medicine, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210028, People's Republic of China.
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View Article and Find Full Text PDFSci Rep
January 2025
Department of Pediatrics, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe Mikicho, Kidagun, 761-0793, Kagawa, Japan.
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View Article and Find Full Text PDFInflamm Res
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