Inhibition of Yes-Associated Protein by Verteporfin Ameliorates Unilateral Ureteral Obstruction-Induced Renal Tubulointerstitial Inflammation and Fibrosis

被引：29
作者：
Jin, Jixiu [1 ]
Wang, Tian [1 ]
Park, Woong [1 ]
Li, Wenjia [1 ]
Kim, Won [1 ,2 ]
Park, Sung Kwang [1 ,2 ]
Kang, Kyung Pyo [1 ,2 ]
机构：
[1] Jeonbuk Natl Univ, Res Inst Clin Med, Dept Internal Med, Med Sch, Jeonju 54907, South Korea
[2] Jeonbuk Natl Univ Hosp, Biomed Res Inst, Jeonju 54907, South Korea
来源：
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2020年 / 21卷 / 21期
基金：
新加坡国家研究基金会;
关键词：
kidney fibrosis; inflammation; myofibroblast activation; extracellular matrix; Hippo pathway; verteporfin; HIPPO PATHWAY; TGF-BETA; FIBROBLAST ACTIVATION; EXTRACELLULAR-MATRIX; YAP; KIDNEY; MECHANISMS; TAZ; DISRUPTION; RECEPTOR;
D O I：
10.3390/ijms21218184
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Yes-associated protein (YAP) activation after acute ischemic kidney injury might be related to interstitial fibrosis and impaired renal tubular regeneration. Verteporfin (VP) is a photosensitizer used in photodynamic therapy to treat age-related macular degeneration. In cancer cells, VP inhibits TEA domain family member (TEAD)-YAP interactions without light stimulation. The protective role of VP in unilateral ureteral obstruction (UUO)-induced renal fibrosis and related mechanisms remains unclear. In this study, we investigate the protective effects of VP on UUO-induced renal tubulointerstitial inflammation and fibrosis and its regulation of the transforming growth factor-beta 1 (TGF-beta 1)/Smad signaling pathway. We find that VP decreased the UUO-induced increase in tubular injury, inflammation, and extracellular matrix deposition in mice. VP also decreased myofibroblast activation and proliferation in UUO kidneys and NRK-49F cells by modulating Smad2 and Smad3 phosphorylation. Therefore, YAP inhibition might have beneficial effects on UUO-induced tubulointerstitial inflammation and fibrosis by regulating the TGF-beta 1/Smad signaling pathway.
引用
收藏
页码：1 / 15
页数：14
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