ARCHITECTURE AND FIBROTIC PROCESSES IN BOTH STENOTIC AND CONTRALATERAL KIDNEYS

injury (the number of casts/HPF: 2.0 ± 0.7 vs. 0.7 ± 0.1, p < 0.01), and the number of PCNA+ (p < 0.01), TUNEL+ (p < 0.01), and caspase-3+ cells (p < 0.05) were also significantly reduced in the CP+E rats. Furthermore, the CP+E rats had a significant reduction of renal cortical mRNA expression for profibrogenic genes (TGF-β (p < 0.05), collagen type I (p < 0.05), and type III (p < 0.01)) and Bax/Bcl-2 ratio (p < 0.05) compared to the CP-V rats. However, erlotinib treatment did not affect either macrophage infiltration in tubulointerstitium or mRNA expressions for proinflammatory cytokines in CP-N. In vitro, pretreatment of erlotinib significantly reduced the CP-induced phosphorylation of MEK1 (p < 0.01) and Akt (p < 0.01) in HK-2. Conclusions: Erlotinib has renoprotective property that is likely in part through degradation of tubular cell apoptosis and proliferation by inhibiting the downstream signaling pathway of EGFR including MAPK and Akt. Our results suggest that erlotinib may be useful for preventing AKI in patients receiving CP chemotherapy.