Single-nucleotide polymorphisms of the dopamine D2 receptor increase inflammation and fibrosis in human renal proximal tubule cells.

摘要: The dopamine D2 receptor (D2R) negatively regulates inflammation in mouse renal proximal tubule cells (RPTCs), and lack or downregulation of the mice increases vulnerability to independent blood pressure. Some common single-nucleotide polymorphisms (SNPs; rs6276, rs6277, rs1800497) human DRD2 gene are associated with decreased D2R expression function, as well high We tested hypothesis that RPTCs (hRPTCs) expressing these SNPs have increased inflammatory injury markers. studied immortalized hRPTCs carrying compared them no SNPs. had function. expressions proinflammatory tumor necrosis factor-α profibrotic transforming growth factor-β1 its signaling targets Smad3 Snail1 were hRPTC These also showed induction epithelial mesenchymal transition production extracellular matrix proteins, assessed by vimentin, fibronectin 1, collagen I a1. To test specificity SNP effects, transfected a plasmid encoding wild-type DRD2. was factor-β1, Smad3, Snail1, a1 hRPTC-D2R empty vector. data support function has protective effects suggest carriers may be prone chronic disease