Figure 3.

mRNA expression of hypertrophy-modulating genes VDR, AGT, FGFR4, and calcineurin/NFAT target genes RCAN1 and TRPC6 in the myocardium of rats after 4 weeks of renal ablation. 5/6Nx, 5/6 Nephrectomy; No Rx, untreated uremic control group; Pc, paricalcitol; PD, PD173074 pan-FGFR blocker. (a) The reduced VDR expression in the Nx untreated group (n = 5) compared with sham (n = 4) was corrected by treatment with Pc alone (n = 5) (*P < 0.05 vs. untreated Nx) or Pc in tandem with PD (n = 5), while PD blocker alone (n = 5) had no measured effects on VDR mRNA levels. (b) AGT mRNA levels, markedly upregulated by renal ablation in untreated animals (n = 4) compared with sham (n = 4), were suppressed by Pc alone (n = 4) (*P < 0.05) or when administered in tandem with PD (n = 4) (**P < 0.01) compared with untreated Nx animals, as well as by blocker alone (n = 4) (**P < 0.01 vs. untreated Nx). (c) FGFR4 expression, markedly elevated in the myocardium of untreated uremic rats (n = 4) compared with sham (n = 5), was effectively downregulated by PD alone (n = 5) (*P < 0.05 vs. untreated Nx), remained essentially unmodified by Pc alone (n = 5) and declined less robustly by Pc in tandem with PD (n = 4). (d) Compared with sham (n = 6), RCAN1 was upregulated in untreated Nx (n = 6), and effectively and similarly attenuated by treatment with Pc alone (n = 5) and PD alone (n = 5) (both **P < 0.01 vs. untreated Nx). Downregulation of RCAN1 mRNA was amplified when both Pc and PD were administered in tandem (n = 5) (***P < 0.001). (e) Upregulated TRPC6 mRNA levels in the untreated Nx animals (n = 8) compared with sham (n = 5) (*P < 0.05 vs. sham) were reduced most effectively with PD alone (n = 6) (**P < 0.01) or in tandem with Pc (n = 6) (*P < 0.05), and more modestly with Pc alone (n = 5). Data are mean ± SEM. Abbreviations: AGT, Angiotensinogen; FGFR, fibroblast growth factor; VDR, vitamin D receptor.