Department of Internal Medicine, Research Institute of Clinical Medicine, Jeonbuk National University Medical School, Jeonju 54907, Korea.
Biomedical Research Institute, Jeonbuk National University Hospital, Jeonju 54907, Korea.
Int J Mol Sci. 2020 Oct 31;21(21):8184. doi: 10.3390/ijms21218184.
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.
Yes 相关蛋白 (YAP) 在急性肾缺血损伤后的激活可能与间质纤维化和肾小管再生受损有关。维替泊芬 (VP) 是一种光动力疗法中用于治疗年龄相关性黄斑变性的光敏剂。在癌细胞中，VP 可抑制 TEA 结构域家族成员 (TEAD)-YAP 相互作用，而无需光刺激。VP 在单侧输尿管梗阻 (UUO) 诱导的肾纤维化及其相关机制中的保护作用尚不清楚。在这项研究中，我们研究了 VP 对 UUO 诱导的肾小管间质性炎症和纤维化的保护作用及其对转化生长因子-β1 (TGF-β1)/Smad 信号通路的调节作用。我们发现，VP 可降低 UUO 诱导的小鼠肾小管损伤、炎症和细胞外基质沉积的增加。VP 还通过调节 Smad2 和 Smad3 磷酸化，减少 UUO 肾脏和 NRK-49F 细胞中的肌成纤维细胞激活和增殖。因此，YAP 抑制可能通过调节 TGF-β1/Smad 信号通路对 UUO 诱导的肾小管间质性炎症和纤维化产生有益影响。
