Inhibition of Yes-Associated Protein by Verteporfin Ameliorates Unilateral Ureteral Obstruction-Induced Renal Tubulointerstitial Inflammation and Fibrosis.
Jixiu JinTian WangWoong ParkWenjia LiWon KimSung Kwang ParkKyung Pyo KangPublished in: International journal of molecular sciences (2020)
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-β1 (TGF-β1)/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-β1/Smad signaling pathway.
Keyphrases
- transforming growth factor
- epithelial mesenchymal transition
- high glucose
- signaling pathway
- oxidative stress
- diabetic rats
- photodynamic therapy
- induced apoptosis
- drug induced
- extracellular matrix
- stem cells
- endothelial cells
- type diabetes
- metabolic syndrome
- skeletal muscle
- blood brain barrier
- pi k akt
- cell death
- liver fibrosis
- adipose tissue
- cell cycle arrest
- stress induced
- cerebral ischemia