Schema of the protective effect of the D2R on fibrosis in human renal proximal tubule cells (RPTCs).
The effect of the D2R is mediated by regulation of miR-217 expression. Decreased D2R expression/function, as observed in RPTCs, bearing D2R rs6276, rs6277, and rs1800497 alleles, results in decreased miR-217 expression which releases the repressor effect of miR-217 on Wnt5a. Increased expression of Wnt5a and its receptor Ror2 increases the expression of TGFβ1 through the non-canonical pathway, resulting in epithelial mesenchymal transition (EMT), demonstrated by the presence of the EMT markers MMP3, FN1, and Col1a.