G Protein-Coupled Receptor 37L1 Modulates Epigenetic Changes in Human Renal Proximal Tubule Cells

Authors

Ines Armando, Division of Renal Diseases & Hypertension, Department of Medicine, The George Washington University, Washington, DC 20037, USA.
Santiago Cuevas, Division of Renal Diseases & Hypertension, Department of Medicine, The George Washington University, Washington, DC 20037, USA.
Caini Fan, Division of Renal Diseases & Hypertension, Department of Medicine, The George Washington University, Washington, DC 20037, USA.
Megha Kumar, Division of Renal Diseases & Hypertension, Department of Medicine, The George Washington University, Washington, DC 20037, USA.
Zahra Izzi, Division of Renal Diseases & Hypertension, Department of Medicine, The George Washington University, Washington, DC 20037, USA.
Pedro A. Jose, Division of Renal Diseases & Hypertension, Department of Medicine, The George Washington University, Washington, DC 20037, USA.
Prasad R. Konkalmatt, Division of Renal Diseases & Hypertension, Department of Medicine, The George Washington University, Washington, DC 20037, USA.

Document Type

Journal Article

Publication Date

11-21-2022

Journal

International journal of molecular sciences

Volume

23

Issue

22

DOI

10.3390/ijms232214456

Keywords

DNMT1; ETBR-LP2; G protein-coupled receptor; GPCR; GPR37L1; NHE3 signaling pathway; PI3/AKT/mTOR; blood pressure; epigenetics; hypertension; mass spectrometry; renal proximal tubule; sodium transport

Abstract

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.

APA Citation

Armando, Ines; Cuevas, Santiago; Fan, Caini; Kumar, Megha; Izzi, Zahra; Jose, Pedro A.; and Konkalmatt, Prasad R., "G Protein-Coupled Receptor 37L1 Modulates Epigenetic Changes in Human Renal Proximal Tubule Cells" (2022). GW Authored Works. Paper 1915.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/1915

Department

Medicine