Src family kinases (SFKs), an important group of non-
receptor tyrosine kinases, are suggested to be excessively activated during various types of tissue
fibrosis. The present study investigated the effect of KF-1607, an orally active and a newly synthesized
Src kinase inhibitor (SKI) with proposed low toxicity, in preventing the progression of renal interstitial
fibrosis. Unilateral
ureteral obstruction (UUO) surgery was performed in 6-week-old male C57BL/6 mice to induce renal interstitial
fibrosis. Either KF-1607 (30 mg/kg, oral gavage) or PP2 (2 mg/kg,
intraperitoneal injection), a common experimental SKI, was administered to mice for seven days, started one day prior to surgery. UUO injury-induced SFK expression, including Src, Fyn, and Lyn
kinase. SFK inhibition by KF-1607 prevented the progression of tubular injury in UUO mice, as indicated by decreases in
albuminuria, urinary KIM-1 excretion, and kidney
NGAL protein expression. Renal tubulointerstitial
fibrosis was attenuated in response to KF-1607, as shown by decreases in α-SMA,
collagen I and IV
protein expression, along with reduced Masson's trichrome and
collagen-I staining in kidneys. KF-1607 also inhibited
inflammation in the UUO kidney, as exhibited by reductions in F4/80 positive-staining and
protein expression of p-NFκB and ICAM. Importantly, the observed effects of KF-1607 were similar to those of PP2. A new pan
Src kinase inhibitor, KF-1607, is a potential
pharmaceutical agent to prevent the progression of renal interstitial
fibrosis.