School of Medicine and Health Sciences Poster Presentations
G-Protein Coupled Receptor GPR37L1 Regulates Sodium Reabsorption in Renal Proximal Tubule Cells
Poster Number
237
Document Type
Poster
Publication Date
3-2016
Abstract
GPR37L1 is expressed mainly in brain glial cells and muscle-myenteric nerve layers in the gastrointestinal tract. GPR37L1 transgenic mice have decreased systolic blood pressure (SBP), whereas GPR37L1 KO mice have increased SBP. The kidney is critical in the regulation of BP but there are no studies reporting the kidney expression and renal function of GPR37L1. Immunostaining and immunoblotting showed that GPR37L1 is expressed in the apical membrane of proximal tubules of the mouse kidney; RT-PCR of renal proximal tubule and collecting duct cells obtained by laser capture micro-dissection of mouse kidney sections, confirmed these findings. In addition, chronic high salt diet increased the renal expression of prosaposin, a precursor for saposin C, a natural ligand for GPR37L1. Infusion of prosaptide, a synthetic ligand for GPR37L1, decreased SBP in mice by 10 ± 2.8 mm Hg. To determine the roles of GPR37L1 in renal sodium transport, we over-expressed the protein in human renal proximal tubule (RPT) cells (n=3). Intracellular sodium was increased in GPR37L1-transfected RPT cells (3.2 ± 0.6 fold , P<0.001) compared with mock-transfected cells. Immunoblot analyses showed increased phosphorylation of Erk1/2 (1.52 ± 0.06 fold, P<0.05), and ribosomal S6 protein (1.39 ± 0.08 fold, P<0.01) in RPT cells over-expressing GPR37L1. Na+,K+-ATPase expression was decreased by 29% ± 3.5 (P<0.05) in GPR37L1-transfected RPT cells. Taken together, these results show that GPR37L1 is expressed in RPT cells and signal via the Erk1/2 pathway. GPR37L1 increases intracellular sodium in RPT cells by decreasing the exit of sodium due to a decrease in Na+,K+-ATPase expression and activity at the basolateral membrane. These results indicate that GPR37L1 may play a role in sodium transport in RPT cells and may be novel targets to designing drugs to treat patients with hypertension.
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Open Access
1
G-Protein Coupled Receptor GPR37L1 Regulates Sodium Reabsorption in Renal Proximal Tubule Cells
GPR37L1 is expressed mainly in brain glial cells and muscle-myenteric nerve layers in the gastrointestinal tract. GPR37L1 transgenic mice have decreased systolic blood pressure (SBP), whereas GPR37L1 KO mice have increased SBP. The kidney is critical in the regulation of BP but there are no studies reporting the kidney expression and renal function of GPR37L1. Immunostaining and immunoblotting showed that GPR37L1 is expressed in the apical membrane of proximal tubules of the mouse kidney; RT-PCR of renal proximal tubule and collecting duct cells obtained by laser capture micro-dissection of mouse kidney sections, confirmed these findings. In addition, chronic high salt diet increased the renal expression of prosaposin, a precursor for saposin C, a natural ligand for GPR37L1. Infusion of prosaptide, a synthetic ligand for GPR37L1, decreased SBP in mice by 10 ± 2.8 mm Hg. To determine the roles of GPR37L1 in renal sodium transport, we over-expressed the protein in human renal proximal tubule (RPT) cells (n=3). Intracellular sodium was increased in GPR37L1-transfected RPT cells (3.2 ± 0.6 fold , P<0.001) compared with mock-transfected cells. Immunoblot analyses showed increased phosphorylation of Erk1/2 (1.52 ± 0.06 fold, P<0.05), and ribosomal S6 protein (1.39 ± 0.08 fold, P<0.01) in RPT cells over-expressing GPR37L1. Na+,K+-ATPase expression was decreased by 29% ± 3.5 (P<0.05) in GPR37L1-transfected RPT cells. Taken together, these results show that GPR37L1 is expressed in RPT cells and signal via the Erk1/2 pathway. GPR37L1 increases intracellular sodium in RPT cells by decreasing the exit of sodium due to a decrease in Na+,K+-ATPase expression and activity at the basolateral membrane. These results indicate that GPR37L1 may play a role in sodium transport in RPT cells and may be novel targets to designing drugs to treat patients with hypertension.
Comments
Presented at: GW Research Days 2016