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Keratinocyte growth factor ameliorates cyclophosphamide-induced ulcerative hemorrhagic cystitis
T R Ulich1, L Whitcomb, W Tang
1Amgen, Inc., Thousand Oaks, California 91320, USA.
Abstract:
To determine whether keratinocyte growth factor (KGF), an epithelial and 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 were evaluated histologically 48 h after CP injection, and KGF pretreatment was found to almost completely prevent CP-induced ulcerative hemorrhagic cystitis. Urinary KGF levels were measured by ELISA, and KGF was found to be undetectable in control urine, but it was found to appear in the urine of KGF-treated rats at 8 h, with a peak concentration of approximately 10 ng/ml. Bilateral nephrectomy did not diminish the proliferative effect of KGF on urothelium, suggesting that the contribution of urinary KGF to urothelial proliferation is insignificant. In conclusion, systemic administration of KGF is protective against CP-induced cystitis. Although KGF appears in the urine, urinary KGF is not necessary for the proliferative action of KGF on urothelium.