Figure 3.

Podocyte-specific overexpression of VEGF-A₁₆₅b reduces albuminuria in the dual insult of VEGF-A₁₆₄a overexpression and STZ-induced diabetic nephropathy. (A) Heterozygous mice overexpressing human VEGF-A₁₆₅b in podocytes (blue: neph^hVEGF-A₁₆₅b) were crossed with mice in which murine VEGF-A₁₆₄a (^mVEGF-A₁₆₄a) overexpression in podocytes could be induced with doxycycline (dox): heterozygous podocin-rtTA:TetO-^mVEGF-A₁₆₄a mice (red: pod-TetO-^mVEGF-A₁₆₄a), to generate mice co-overexpressing ^mVEGF-A₁₆₄a and ^hVEGF-A₁₆₅b in podocytes. Offspring were treated with STZ at 12 weeks of age to induce diabetes in all groups. After 5 weeks of diabetes, all mice received doxycycline, inducing ^mVEGF-A₁₆₄a overexpression in the two groups carrying the podocin-rtTA:TetO-^mVEGF-A₁₆₄a transgene. After 1 week of doxycycline treatment, urinary albumin-to-creatine ratio (uACR) was measured and compared with uACR obtained before doxycycline administration. (B) Change in uACR after 7 days of doxycycline treatment in diabetic mice with no transgenes, diabetic mice overexpressing ^hVEGF-A₁₆₅b alone, diabetic mice overexpressing ^mVEGF-A₁₆₄a alone, and diabetic mice co-overexpressing ^mVEGF-A₁₆₄a and ^hVEGF-A₁₆₅b. Dashed line represents no change in albuminuria during the 1-week doxycycline treatment period. n=3–6 mice per group. Error bars, SEM. *P<0.05, one-way ANOVA.