Figure 1

Complement activation via AP causes podocyte depletion in mice with protein-overload proteinuria.

(A) Quantification of WT1-positive podocytes expressed as number per glomerulus in Cfh^−/−, Bf^−/− mice and the corresponding WT littermates receiving saline or BSA (n = 5 mice/group), evaluated on day 23 after starting BSA. *P < 0.05, **P < 0.01 versus corresponding saline; ^°P < 0.05 vs corresponding WT+BSA. (B) Urinary albumin/creatinine ratio measured on day 23 after starting BSA in WT, Cfh^−/− and Bf^−/− mice receiving saline or BSA. **P < 0.01 versus corresponding saline; °°P < 0.01 vs corresponding WT+BSA (n = 4 WT mice treated with saline or BSA, n = 5 Cfh^−/− +saline mice, n = 6 Cfh^−/− +BSA mice and n = 5 Bf^−/− mice treated with saline or BSA). (C) Representative images showing glomerular C3 deposits (green) in WT, Cfh^−/− or Bf^−/− mice injected with saline or BSA. Scale bars: 20 μm. (D) Quantification of C3 staining expressed as percentage of positive glomerular area. *P < 0.05, **P < 0.01 versus corresponding saline; ^§P < 0.0001 versus corresponding WT+saline, °P < 0.01, °°P < 0.0001 versus corresponding WT+BSA (n = 4 WT mice treated with saline or BSA, n = 5 Cfh^−/− mice treated with saline or BSA and n = 5 Bf^−/− mice treated with saline or BSA). (E) Representative images of renal tissue from WT and Cfh^−/− +BSA mice showing merged area (yellow) of costaining of glomerular C3 deposits (green) and nephrin (red) in podocytes. Insets display enlarged images. Nuclei are counterstained with DAPI. Scale bars: 20 μm. Data information: Values are presented as mean ± SEM. ANOVA corrected with Tukey (B) or Bonferroni (A,C,D,E) coefficient.