Tesevatinib ameliorates progression of polycystic kidney disease in rodent models of autosomal recessive polycystic kidney disease

Figure 10 Target validation in BPK. Western analysis of the MAPK pathway activity of EGFR (p-EGFR), cSrc (pSrc), and ERK1/2 (p-ERK ½) reveals that BPK cystic kidneys have significantly increased levels of active or phosphorylated p-EGFR (A2), pSrc (C2) and ERK1/2 (E2) compared to wild-type BALB/c control levels in lanes (A1, C1 and E1) respectively. TSV treatment at 7.5 or 15 mg/kg per day resulted in a dose dependent reduction in the phosphorylation or activity of p-EGFR (A3 and A4), and p-Src (C3 and C4) that correlated directly to a reduction in the activity of ERK1/2 (p-ERK1/2: E3 and E4).The reduced level of phosphorylated proteins occurred without changes in the level of total EGFR (B2, B3 and B4), total Src (D2, D3 and D4) or total ERK1/2 (F2, F3 and F4). The numbers below the band in each lane represents the average ± SD (n = 3) of the relative density of each band when normalized to the wildtype BALB/c control value arbitrarily set at 1.