Renoprotective effects of a factor Xa inhibitor: fusion of basic research and a database analysis

Figures

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  Figure 1. Expression of coagulation factors and protease-activated receptors (PARs) in the kidney. Changes in the mRNA levels of (a) FX and TF, and (b) Par1 and Par2 at day 7 in the kidneys of mice that received a sham operation with vehicle (sham; white bar) or unilateral ureteral obstruction (UUO) with vehicle (UUO; black bar). The values are expressed as means ± standard error of the mean (SEM). *p < 0.05, **p < 0.01 vs. sham mice; n = 7–8. (c) Representative immunohistochemical results for PAR antibodies 7 days after operation.

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  Figure 2. Effect of edoxaban on unilateral ureteral obstruction (UUO) -induced renal interstitial fibrosis. (a) Upper panel, representative histological findings in renal tissue stained with Picrosirius Red 7 days after operation; Lower panel, quantitative analysis of renal interstitial fibrosis at day 7. Sham operation with vehicle (sham; white bar), UUO with vehicle (UUO; black bar), and UUO with 50 mg/kg/day edoxaban (UUO + EDO; grey bar). Results are expressed as means ± standard error of the mean (SEM). *p < 0.05, **p < 0.01; n = 4–9 per group. (b) Changes in the mRNA levels of Col1, Col3, and Fn in the kidneys of mice at day 7. Results are expressed as means ± SEM. **p < 0.01. n = 8–13 per group.

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  Figure 3. Renal interstitial macrophage infiltration and inflammatory cytokines. (a) Upper panel, representative immunohistochemical results for F4/80 antibodies 7 days after operation; Lower panel, quantitative analysis of the F4/80-positive area within the interstitial area at day 7. Sham operation with vehicle (sham; white bar), unilateral ureteral obstruction (UUO) with vehicle (UUO; black bar), and UUO with 50 mg/kg/day edoxaban (UUO + EDO; grey bar). Results are expressed as means ± standard error of the mean (SEM). *p < 0.05, **p < 0.01; n = 6–7 per group. (b) Changes in the mRNA levels of F4/80, tumour necrosis factor α (Tnfα), and interleukin-10 (IL10) in the kidneys of mice at day 7. Results are expressed as means ± SEM. *p < 0.05, **p < 0.01; n = 5–13 per group. (c) Changes in the mRNA levels of monocyte chemotactic protein (Mcp1), and interleukin-1β (IL1β) in the kidneys of mice at day 7. Results are expressed as means ± SEM. **p < 0.01. n = 6–13 per group. (d) Upper panel, representative images of MCP-1 and IL-1β protein staining in the kidney; Lower panel, semi-quantitative analysis of MCP-1 and IL-1β expression by densitometry (full-length blots are presented as…

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  Figure 4. Effect of edoxaban on mRNA levels of transforming growth factor β (TGF-β) and α-smooth muscle actin (αSMA), a myofibroblast marker. Changes in the mRNA expression levels of Tgfb (a) and Acta2 (b) in the kidneys of mice at day 7. Sham operation with vehicle (sham; white bar), unilateral ureteral obstruction (UUO) with vehicle (UUO; black bar), and UUO with 50 mg/kg/day edoxaban (UUO + EDO; grey bar). Results are expressed as means ± standard error of the mean (SEM). **p < 0.01. n = 8–13 per group.