Figure 7. SIRPα critically controls podocyte stress adaptation through promotion of autophagy in vivo.

(A) GFP-LC3–positive autophagosomes in GFP-LC3–transgenic mice (GFP-LC3) and Sirpa^–/– mice crossed with GFP-LC3-transgenic mice (Sirpa^–/–GFP-LC3, with proteinuria, 20 months). Arrows indicate autophagosomes. The histogram represents statistical autophagosomes in each group. n = 5 each group of mice and 6–10 glomeruli from each mouse were analyzed. (B) Accumulation of the ubiquitin-associated protein p62 in 20-month-old GFP-LC3 and Sirpa^–/–GFP-LC3 mice (arrows indicate podocytes). (C) Western blot analysis of p62 in glomerulus of 20-month-old GFP-LC3 and Sirpa^–/–GFP-LC3 mice. Immunoblots are representative of 3 independently performed experiments. The histogram represents statistical results from 3 independently performed experiments. (D) GFP-LC3–positive autophagosomes in 8-week-old GFP-LC3–transgenic mice and Sirpa^–/–GFP-LC3 mice treated with PAN, ADR, or STZ; arrows indicate autophagosomes. The histograms represent statistical autophagosomes in each group. n = 3 each group of mice and 10 glomeruli from each mouse were analyzed. (E) Accumulation of p62 in 8-week-old GFP-LC3 and Sirpa^–/–GFP-LC3 mice treated with PAN for 2 weeks (2W), ADR for 4 weeks, and STZ for 6 weeks (arrows indicate podocytes). (F) Western blotting of p62 in glomerulus of 8-week-old GFP-LC3 and Sirpa^–/–GFP-LC3 mice with different treatments. Immunoblots are representative of 3 independently performed experiments. The histogram represents statistical results from 3 independently performed experiments. Scale bars in A, B, D, and E: 10 μm. Data in A, C, D, and F represent mean ± SEM, and P values were analyzed by 2-tailed Student’s t test. *P < 0.05, **P < 0.01.