Figure 6. CD-selective expression of active BRAF increased renal cystic disease and fibrosis and accelerated the decline in kidney function in pcy/pcy mice.
(a) Representative kidney sections from 10-week-old pcy/pcy and pcy/pcy; BRAFLSL-V600E; Pkhd1-Cre (pcy/pcy; BRafCD) mice. Scale bar = 1 mm. Bar graphs represent the mean ± SEM for (b) body weight (BW) and (c) kidney weight (KW), as a percentage of BW [KW/BW (%)], (d) cyst area, relative to total surface area [cystic index (% SA)], and (e) number of cysts in kidney sections from pcy/pcy and pcy/pcy; BRafCD mice. **P < 0.01 and ***P < 0.001, compared to pcy/pcy mice (N = 4–6). (f) Fluorescent images of kidney sections from pcy/pcy and pcy/pcy; BRafCD mice that were stained with PCNA (red), DBA (green) and DAPI (blue). (g) Bar graph displays the mean ± SEM for PCNA-positive cells as a % of total nuclei. *P < 0.05, compared to pcy/pcy kidneys (N = 4) (h) Representative immunoblots for P-ERK, ERK, BRAF, and GAPDH in kidney lysates from pcy/pcy mice without (−) or with (+) CD expression of active BRAF. The numbers above the bands are P-ERK/ERK and BRAF/GAPDH, respectively. (i) The percentage of fibrosis to the surface area (SA) of the entire kidney section (fibrotic index) for pcy/pcy and pcy/pcy; BRafCD kidneys. ***P < 0.001, compared to pcy/pcy (N = 6). (j) BUN levels in pcy/pcy and pcy/pcy; BRafCD mice at 10 weeks of age **P < 0.01, compared to pcy/pcy mice (N = 4).