YY1年
槲皮素
炎症
糖尿病肾病
癌症研究
分子生物学
化学
生物
免疫学
基因表达
发起人
生物化学
内分泌学
肾
抗氧化剂
基因
作者
Tingting Yang,Yinlu Hu,Wenjie Jiang,Jiale Pang,Yequan Zhou,Huanming Zhang,Zeyuan Yin,Zhenzhou Jiang,Sitong Qian,Chujing Wei,Meng Yan,Xia Zhu,Tao Wang,Qian Lü
出处
期刊:Phytomedicine
[Elsevier]
日期:2023-03-01
卷期号:111: 154659-154659
被引量:2
标识
DOI:10.1016/j.phymed.2023.154659
摘要
The emergence of tubulointerstitial inflammation (TI) could accelerate the development of tubulointerstitial fibrosis (TIF) of diabetic nephropathy (DN). Yin Yang 1 (YY1) was a new pro-inflammatory mediator and became the important target of DN-related TIF. Quercetin performed an effective role in anti-inflammation and was probable to bind to YY1. However, the role of YY1 in quercetin's anti-inflammatory effect on DN-related TIF was uncovered.To investigate the potential effect and mechanism of quercetin against DN-related TI.The protein levels of YY1 were examined in the renal tubular epithelial cells (RTECs) of db/db mice and HG-cultured HK-2 cells. Molecular modeling studies and YY1 overexpression lentivirus vector were selected to further confirm the indispensable part of YY1 in quercetin's TI protection in vitro. Luciferase assay and chromatin immunoprecipitation (ChIP) assay were carried out to identify whether YY1 directly regulated IL-6/STAT3 signaling by binding to the IL-6 promoter in quercetin's TI protection in vitro. At last, the important role of YY1-mediated IL-6/STAT3 signaling in quercetin's TIF protection effect was further identified by using of YY1 overexpression lentivirus vector and IL-6 specific inhibitor tocilizumab.Along with the alleviated tubulointerstitial injury by quercetin in the RTECs of db/db mice and HK-2 cells stimulated by HG, YY1-mediated IL-6/STAT-3 pathway involved in TI protection of quercetin in vivo and in vitro. Quercetin bound to YY1 and decreased its protein expression, and YY1 directly suppressed IL-6 transcription by bounding to its promoter, resulting in the alleviation of inflammation by inactivating of IL-6/STAT-3 pathway in vitro. YY1-mediated IL-6/STAT-3 pathway was also indispensable for the alleviation of quercetin on DN-associated TIF.YY1 could not be absent from quercetin's anti-inflammatory effect on DN-associated TIF via alleviating IL-6/STAT-3 pathway mediated TI.
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