Fig 5. JNK inhibition reduces fibrosis in juvenile Pkd2 mutant mice.
Mice with the following genotypes were treated with tamoxifen by maternal transfer at P2-4 and collected at P21: Con (Rosa26-CreERT2; Pkd2fl/+), Pkd2 (Rosa26-CreERT2; Pkd2fl/fl; Jnk1+/+, fl/+; Jnk2+/+, +/-), and Pkd2-Jnk (Rosa26-CreERT2; Pkd2fl/fl; Jnk1fl/fl; Jnk2null/null). (A) Kidney sections from P21 mice were probed for SMA, a marker of active fibroblasts. Nuclei were stained with DAPI. Images were obtained on Zeiss Axio Scan.Z1 with 20X objective. Scale bar is 100 microns. (B) SMA intensity was compared to cystic index for 10 animals per group. SMA mean intensity was measured using ImageJ software and divided by non-cystic area (mean intensity / non-cystic area x 100,000). Cystic index (cystic area / total area x 100%) was determined for DAPI staining using Image J software. Linear regression analysis shows that the difference between slopes for Pkd2 (y = 0.07x-2) and Pkd2-Jnk (y = 0.01x+0.5) approaches but does not reach significance (P = 0.055). (C) Whole kidney protein samples from P21 mice were immunoblotted for SMA and loading control Gapdh. (D) Quantification of immunoblots described in (C). N is 3 animals per groups. ****, P < 0.0001 by one-way ANOVA followed by Tukey multiple comparison test with multiplicity-adjusted p-values. Error bars indicate SD.