任天堂
医学
癌症研究
血小板源性生长因子受体
肾脏疾病
酪氨酸激酶
血管内皮生长因子
原癌基因酪氨酸蛋白激酶Src
纤维化
酪氨酸激酶抑制剂
内科学
特发性肺纤维化
生长因子
受体
癌症
血管内皮生长因子受体
肺
作者
Feng Liu,Li Wang,Hualin Qi,Jun Wang,Yi Wang,Wei Jiang,Liuqing Xu,Na Liu,Shougang Zhuang
出处
期刊:Clinical Science
[Portland Press]
日期:2017-06-24
卷期号:131 (16): 2125-2143
被引量:56
摘要
Nintedanib (BIBF1120) is a triple kinase inhibitor of platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptors (FGFR), vascular endothelial growth factor receptor (VEGFR), and Src family kinase, which has recently been approved by FDA to treat idiopathic pulmonary fibrosis. Whether it affects renal fibrosis remains unknown. Here, we demonstrated that administration of nintedanib immediately or 3 days after unilateral ureteral obstruction (UUO) injury and with folic acid (FA) injection attenuated renal fibrosis and inhibited activation of renal interstitial fibroblasts. Delayed administration of nintedanib also partially reversed established renal fibrosis. Treatment with nintedanib blocked UUO-induced phosphorylation of PDGFRβ, FGFR1, FGFR2, VEGFR2, and several Src family kinases including Src, Lck, Lyn as well as activation of signal transducer and activator of transcription-3 (STAT3), nuclear factor-κB (NF-κB), and Smad-3 in the kidney. Furthermore, nintedanib inhibited UUO-elicited renal proinflammatory cytokine expression and macrophage infiltration. These data indicate that nintedanib is a potent anti-fibrotic agent in the kidney and may hold therapeutic potential as a treatment of chronic fibrotic kidney disease.
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