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KF-1607, a novel pan src kinase inhibitor, attenuates obstruction-induced tubulointerstitial fibrosis in mice

Title
KF-1607, a novel pan src kinase inhibitor, attenuates obstruction-induced tubulointerstitial fibrosis in mice
Authors
Dorotea D.Lee S.Lee S.J.Lee G.Son J.B.Choi H.G.Ahn S.-M.Ha H.
Ewha Authors
하헌주
SCOPUS Author ID
하헌주scopus
Issue Date
2021
Journal Title
Biomolecules and Therapeutics
ISSN
1976-9148JCR Link
Citation
Biomolecules and Therapeutics vol. 29, no. 1, pp. 41 - 51
Keywords
Chronic kidney diseaseRenal fibrosisSrc kinaseSrc kinase inhibitorUreteral obstruction
Publisher
Korean Society of Applied Pharmacology
Indexed
SCIE; SCOPUS; KCI scopus
Document Type
Article
Abstract
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. © 2021 The Korean Society of Applied Pharmacology.
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DOI
10.4062/biomolther.2020.088
Appears in Collections:
약학대학 > 약학과 > Journal papers
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