Regulon analysis identifies protective FXR and CREB5 in proximal tubules in early diabetic kidney disease.
Regulon analysis identifies protective FXR and CREB5 in proximal tubules in early diabetic kidney disease.
复制标题
DOI：
10.1186/s12882-023-03239-6
复制
发表时间：
2023-06-19
期刊：
影响因子：
2.3
通讯作者：
Shi, Jingsong
中科院分区：
文献类型：
--
作者：
Shi, Wanting;Le, Weibo;Tang, Qiaoli;Shi, Shaolin;Shi, Jingsong
关键词：
糖尿病肾病（DKD）是糖尿病最常见的并发症，也是世界范围内肾衰竭的主要原因。尽管它很普遍，但DKD早期肾脏损害的机制仍然知之甚少。在这项研究中，我们使用单核RNA-seq技术构建了早期DKD患者肾皮质的基因调控网络（grn）。通过将这些网络与健康对照进行比较，我们确定了与糖尿病状态相关的遗传调控的细胞类型特异性变化。FXR （NR1H4）和CREB5的调控活性在肾近曲小管上皮细胞（PCTs）中被发现上调，通过DKD患者肾活检的免疫荧光染色证实了这一点。体外培养的HK2细胞实验表明，FXR和CREB5对细胞凋亡和上皮间质转化有保护作用。我们的研究结果表明，FXR和CREB5可能是DKD患者早期干预的有希望的靶点。在线版本包含补充材料，可在10.1186/s12882-023-03239-6获得。
Diabetic kidney disease (DKD) is the most common complication of diabetes mellitus and a leading cause of kidney failure worldwide. Despite its prevalence, the mechanisms underlying early kidney damage in DKD remain poorly understood. In this study, we used single nucleus RNA-seq to construct gene regulatory networks (GRNs) in the kidney cortex of patients with early DKD. By comparing these networks with those of healthy controls, we identify cell type-specific changes in genetic regulation associated with diabetic status. The regulon activities of FXR (NR1H4) and CREB5 were found to be upregulated in kidney proximal convoluted tubule epithelial cells (PCTs), which were validated using immunofluorescence staining in kidney biopsies from DKD patients. In vitro experiments using cultured HK2 cells showed that FXR and CREB5 protected cells from apoptosis and epithelial–mesenchymal transition. Our findings suggest that FXR and CREB5 may be promising targets for early intervention in patients with DKD. The online version contains supplementary material available at 10.1186/s12882-023-03239-6.
登录
查看更多内容
影响因子：
10.5
作者：
Cabili, Moran N.;Trapnell, Cole;Rinn, John L.
通讯作者：
Rinn, John L.
影响因子：
9
作者：
Kim DH;Park JS;Choi HI;Kim CS;Bae EH;Ma SK;Kim SW
通讯作者：
Kim SW
影响因子：
16.6
作者：
Lake, Blue B.;Chen, Song;Jain, Sanjay
通讯作者：
Jain, Sanjay
LncRNA Gas5 通过 Creb5 调节肾纤维化中的 Fn1 沉积
影响因子：
3.8
作者：
Su, Huanhou;Xie, Jingzhou;Wang, Lijing
通讯作者：
Wang, Lijing
DOI：
10.1152/ajprenal.00406.2005
发表时间：
2006-05-01
影响因子：
4.2
作者：
Docherty, NG;O'Sullivan, OE;Watson, RWG
通讯作者：
Watson, RWG