FIGURE 1.

Podocyte VEGF knockdown (VEGF^KD ) prevents glomerular hypertrophy in diabetic mice. (A) VEGF^KD Transgenic mouse line carries 4 transgenes: Nphs2-rtTA and tet-0-shVEGF that are activated by doxycycline to synthesize shRNA targeting Vegf-a exon 1, which inhibits expression of all Vegf-a isoforms in podocytes (Veron et al., 2012). (B) VEGF^KD mice received STZ (50 mg IP, 5 daily doses) (DM-VEGF^KD − dox), STZ + doxycycline (DM-VEGF^KD + dox), doxycycline (VEGF^KD + dox) or no treatment (VEGF^KD − dox). Dox was started a week after STZ, 2 weeks later was considered time 0 (when random blood glucose was steadily elevated) for DM-VEGF^KD mice; (C) non-diabetic control glomerulus (VEGF^KD − dox) shows normal histology; (D) diabetic control (DM-VEGF^KD − dox) glomerulus shows hypertrophy and mesangial expansion; (E) non-diabetic VEGF^KD (+ dox) glomerulus is smaller than control (C, − dox); (F) diabetic VEGF^KD (+ dox) glomerulus shows diffuse glomerulosclerosis and is smaller than control (D, − dox); Scale bars = 50 μm; (G) quantitation of glomerular size demonstrates significantly smaller glomerular volume in VEGF^KD (+ dox) vs. control (−dox) glomeruli from non-diabetic (VEGF^KD ) and diabetic (DM-VEGF^KD ) mice; unpaired t-test with Welch’s correction was used; asterisk (*) indicates p < 0.05, (***) indicates p < 0.001; control vs. VEGF^KD or non-diabetic vs. diabetic, as indicated; non-DM, non-diabetic mice, DM, diabetic mice; dox, uninduced mice; dox, doxycycline- treated mice.