Src family kinases (SFKs), a group of non-receptor tyrosine kinases, has been suggested to mediate the development of fibrosis in various tissues. The present study investigated the effect of KF-1607, 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) or PP2 (2 mg/kg, IP injection), a common experimental SKI, was administered for 7 days, started one day prior to surgery. UUO increased SFKs expression: Src, Fyn, and Lyn. KF-1607 restored renal function and attenuated tubular injury, indicated by decreases in albuminuria, urinary KIM-1, and NGAL protein level in the kidney. Renal interstitial fibrosis was halted in response to KF-1607, as shown by decreases in α-SMA, collagen I and IV protein levels, and matrix accumulation in tubulointerstitial area. KF-1607 also inhibited inflammation in the UUO kidney, exhibited by reductions in F4/80 positive-stained area and protein levels of p-NFκB and ICAM. Importantly, the observed effects of KF-1607 was similar to those of PP2. Altogether, KF-1607 is a promising agent to attenuate the progression of renal interstitial fibrosis.

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