Figure 3.

Exaggerated fibrotic response to the nephrotoxin in endothelial SIRT1-knockout mice. (A) Representative Masson’s trichrome staining of kidney sections demonstrate that at 28 days postinjection (when kidney function is laboratory unperturbed) and at 90 days (when it is perturbed), SIRT1^endo−/− knockout mice show significantly more tubulointerstitial fibrosis than SIRT1^endo+/− heterozygote and SIRT1^Flox/Flox/SIRT1^Flox/WT control animals. (B) Quantification of the fibrotic area. (C–E) Expression of collagen I and collagen III, as well as the expression ratio of short (S)/long (L) endoglin isoforms, examined by quantitative real-time PCR 90 days after folic acid treatment show significant increase in SIRT1^endo−/− mice. The animals in treatment groups are injected with 250 mg/kg folic acid in 0.3 M NaHCO₃ vehicle and euthanized after 28 or 90 days. Untreated mice are injected with vehicle only and euthanized after 90 days. n=6–7 per group. Data are the mean ± SEM. *P<0.05 treated versus untreated animals; ^#P<0.05 SIRT1^endo−/− versus other treated groups after 90 days and SIRT1^endo+/− versus SIRT1^Flox/WT after 90 days. Original magnification, ×100.