Chymase Inhibition Attenuates Kidney Fibrosis in a Chronic Mouse Model of Renal Ischemia–Reperfusion Injury

Figures

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  Figure 1. Changes in kidney surface color during ischemia (A) and reperfusion (B).

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  Figure 2. Changes in BW and KW 6 weeks after the sham operation or I/R injury. Representative photographs of the right and left kidneys 6 weeks after surgery from a sham-operated mouse (A), and from I/R mice treated with a placebo (B) and TY-51469 (C). (D) Changes in BW 6 weeks after the sham operation or after the I/R injury. (E) Changes in the ratio of KW to BW 6 weeks after the sham operation or I/R. $$$ p < 0.001 vs. the non-ischemic contralateral kidney. ## p < 0.01 vs. the sham-operated right kidney. *** p < 0.001 vs. the sham-operated left kidney.

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  Figure 3. Azan–Mallory staining and quantification of renal fibrotic areas. Representative images of Azan–Mallory-stained cross-sections from a sham-operated mouse (A) and from an I/R mouse treated with a placebo (B) and TY-51469 (C). The blue-stained areas represent collagen deposition. (D) Quantification of renal interstitial fibrotic areas in cross-sections of kidneys from sham-operated mice or I/R mice treated with a placebo and TY-51469. $ p < 0.05, $$$ p < 0.001 vs. the non-ischemic contralateral kidney. Bar indicates 200 μm. * p < 0.05, *** p < 0.001 vs. the sham-operated left kidney. ## p < 0.01 vs. the placebo-treated left kidney.

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  Figure 4. Toluidine blue staining and quantification of mast cells. Representative images of toluidine blue-stained cross-sections of the kidneys of a sham-operated mouse (A) and I/R mouse treated with a placebo (B) and TY-51469 (C). Mast cells are indicated by black arrows. (D) Quantification of mast cells in cross-sections of kidneys from sham-operated mice and I/R mice treated with a placebo and TY-51469. $$$ p < 0.001 vs. the non-ischemic contralateral kidney. * p < 0.05, *** p < 0.001 vs. the sham-operated left kidney. # p < 0.05 vs. the placebo-treated left kidney.

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  Figure 5. Chymase immunostaining and quantification of chymase-positive cells. Representative images of chymase-immunostained cross-sections from a sham-operated mouse (A) and from I/R mice treated with a placebo (B) and TY-51469 (C). Chymase-positive cells are indicated by black arrows. (D) Quantification of chymase-positive cells in cross-sections of kidneys from sham-operated mice and I/R mice treated with a placebo and TY-51469. $$$ p < 0.001 vs. the non-ischemic contralateral kidney. *** p < 0.001 vs. the sham-operated left kidney. ### p < 0.001 vs. the placebo-treated left kidney.

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  Figure 6. Changes in MMCP-4 (A), TGF-β1 (B), and collagen I (C), mRNA expression 6 weeks after the sham operation or I/R. $ p < 0.05, $$$ p < 0.001 vs. the non-ischemic contralateral kidney. * p < 0.05, ** p < 0.01, *** p < 0.001 vs. the sham-operated left kidney. # p < 0.05, ## p < 0.01 vs. the placebo-treated left kidney.

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  Figure 7. Linear regression analyses of mRNA expression levels of MMCP-4, TGF-β1, and collagen I. Correlations were observed between MMCP-4 and TGF-β1 mRNA levels (A), MMCP-4 and collagen I mRNA levels (B), and TGF-β1 and collagen I mRNA levels (C) in all the examined kidneys 6 weeks after surgery.