School of Medicine and Health Sciences Poster Presentations

Title

Dopamine D2 Receptors Regulate Wnt3 Signaling and Apoptosis in Human Renal Proximal Tubule Cells

Poster Number

153

Document Type

Poster

Publication Date

3-2016

Abstract

Lack or downregulation of the dopamine D2 receptor (D2R) increases renal reactive oxygen species (ROS) production and vulnerability to renal inflammation in human renal proximal tubule cells (hRPTCs). Common single nucleotide polymorphisms (SNPs) rs6276, 6277, and 1800497 in the D2R gene (DRD2) are associated with decreased D2R expression and function. In hRPTCs carrying these DRD2 SNPs, there is increased expression of profibrotic factors, production of extracellular matrix (ECM), and apoptosis. We hypothesized that the D2R plays a pivotal role in protecting hRPTCs from apoptosis and fibrosis by regulating Wnt3 signaling. hRPTC-DRD2 SNPs cause activation of Wnt3/β-catenin pathway, proved by decreased β-catenin phosphorylation and increased expression of downstream pro-apoptotic factors Bax and FasL. Silencing D2R by DRD2 siRNA activated β-catenin by decreasing its phosphorylation in hRPTC-D2R wild-type (WT), resulting in increased Bax and FasL expressions. These findings were reversed, including the decreased Wnt3 mRNA and protein expression in hRPTC-DRD2 SNPs transfected with WT DRD2 plasmid. Compared with those observed with transfection of DRD2 plasmid, stimulation with the selective D2R agonist quinpirole produced the same effects. We also found that hRPTC-DRD2 SNPs treated with Wnt3 siRNA prevented the increase in Bax and FasL but increased the protein expression of anti-apoptotic factors cFlar and Birc5, and decreased the number of apoptotic cells. These data show that apoptosis is increased and the Wnt3/β-catenin signals are activated in hRPTC-DRD2 SNPs.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Open Access

1

Comments

Presented at: GW Research Days 2016

This document is currently not available here.

Share

COinS
 

Dopamine D2 Receptors Regulate Wnt3 Signaling and Apoptosis in Human Renal Proximal Tubule Cells

Lack or downregulation of the dopamine D2 receptor (D2R) increases renal reactive oxygen species (ROS) production and vulnerability to renal inflammation in human renal proximal tubule cells (hRPTCs). Common single nucleotide polymorphisms (SNPs) rs6276, 6277, and 1800497 in the D2R gene (DRD2) are associated with decreased D2R expression and function. In hRPTCs carrying these DRD2 SNPs, there is increased expression of profibrotic factors, production of extracellular matrix (ECM), and apoptosis. We hypothesized that the D2R plays a pivotal role in protecting hRPTCs from apoptosis and fibrosis by regulating Wnt3 signaling. hRPTC-DRD2 SNPs cause activation of Wnt3/β-catenin pathway, proved by decreased β-catenin phosphorylation and increased expression of downstream pro-apoptotic factors Bax and FasL. Silencing D2R by DRD2 siRNA activated β-catenin by decreasing its phosphorylation in hRPTC-D2R wild-type (WT), resulting in increased Bax and FasL expressions. These findings were reversed, including the decreased Wnt3 mRNA and protein expression in hRPTC-DRD2 SNPs transfected with WT DRD2 plasmid. Compared with those observed with transfection of DRD2 plasmid, stimulation with the selective D2R agonist quinpirole produced the same effects. We also found that hRPTC-DRD2 SNPs treated with Wnt3 siRNA prevented the increase in Bax and FasL but increased the protein expression of anti-apoptotic factors cFlar and Birc5, and decreased the number of apoptotic cells. These data show that apoptosis is increased and the Wnt3/β-catenin signals are activated in hRPTC-DRD2 SNPs.