Figure 7.

RIBOTAC 4 prevents Alport mice from progression of disease-associated nephropathy by inhibiting miR-21 biogenesis. (A) In vivo treatment of 4 (56 mg/kg, q.o.d., 42 days) decreased urine albumin concentration, as normalized to urine creatinine in Alport mice. In contrast, 4 had no effect on urine from wild-type (WT) mice. (B) RIBOTAC 4 de-repressed PPARα expression in kidneys of Alport mice, with no significant effect on PPARα expression in WT mice, although abundance was slightly boosted. (C) RIBOTAC 4 decreased pre-miR-21 levels in kidneys of both Alport and WT mice. [Note: Genetic ablation of miR-21 is well tolerated in mice. (12)] (D) Periodic acid–Schiff (PAS) staining shows that RIBOTAC 4 prevented tubule injury observed in Alport mice. Tubule injury severity was scored from 0 to 4 by extent of injury as previously described, (14) where 0 is no tubule injury (top left and right) and 4 is severe injury (bottom left). *p < 0.05, **p < 0.01, ***p < 0.001, as determined by a two-tailed Student’s t test. For vehicle- and 4-treated WT mice, n = 3; for vehicle-treated Alport mice, n = 3; for 4-treated Alport mice, n = 4. All images shown are from biological replicates.