KERATINOCYTE GROWTH-FACTOR AMELIORATES CYCLOPHOSPHAMIDE-INDUCED ULCERATIVE HEMORRHAGIC CYSTITIS

To determine whether keratinocyte growth factor (KGF), an epithelial a nd urothelial growth factor, ameliorates cyclophosphamide (CP)-induced cystitis in rats, KGF (5 mg/kg) was injected in rats as a single i.v. injection 24 h prior to i.p. injection of CP (200 mg/kg). Bladders we re evaluated histologically 48 h after CP injection, and KGF pretreatm ent was found to almost completely prevent CP-induced ulcerative hemor rhagic cystitis, Urinary KGF levels were measured by ELISA, and KGF wa s found to be undetectable in control urine, but it was found to appea r in the urine of KGF-treated rats at 8 h, with a peak concentration o f approximately 10 ng/ml, Bilateral nephrectomy did not diminish the p roliferative effect of KGF on urothelium, suggesting that the contribu tion of urinary KGF to urothelial proliferation is insignificant. In c onclusion, systemic administration of KGF is protective against CP-ind uced cystitis, Although KGF appears in the urine, urinary KGF is not n ecessary for the proliferative action of KGF on urothelium.