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Synergistic Inhibition of Renal Fibrosis by Nintedanib and Gefitinib in a Murine Model of Obstructive Nephropathy by Liu Feng; Wang Li; Yu Chao; Qin Huan; Fang Lu; Wang Yi; Wang Jun; Cui Binbin; Liu Na; Zhuang Shougang is a Medicine article available to read on EtoBox.

What is Synergistic Inhibition of Renal Fibrosis by Nintedanib and Gefitinib in a Murine Model of Obstructive Nephropathy about?

**__Background:__** Our recent studies demonstrated that both nintedanib, an FDA-approved quadruple kinase inhibitor, and gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, protect against obstructive kidney disease. It remains unknown whether they have a synergistic effect. **__Methods:__** In this study, we investigated the effect of combined administration of nintedanib and gefitinib on renal fibrosis in a murine model of renal fibrosis induced by unilateral ureteral obstruction (UUO). **__Results:__** Combined treatment with nintedanib and gefitinib after UUO resulted in a greater antifibrotic effect compared with their individual application. Mechanistically, administration of nintedanib blocked UUO-induced phosphorylation of multiple kinase receptors associated renal fibrosis, including platelet-derived growth factor receptors, fibroblast growth factor receptors, vascular endothelial growth factor receptors, and Src family kinase, while gefitinib inhibited EGFR phosphorylation. Their combination also exhibited a more pronounced effect in reducing expression of tissue inhibitors of metalloproteinase-2 (TIMP-2), increasing expression of matrix metalloproteinase-2

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Author

Liu Feng; Wang Li; Yu Chao; Qin Huan; Fang Lu; Wang Yi; Wang Jun; Cui Binbin; Liu Na; Zhuang Shougang

Publisher

S. Karger AG (ISSN 2296-9381)

Published

2020

Language

EN

Field

Medicine (Health Sciences)