Traditional Chinese Medicine Integrated Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou 450052, P.R. China.
Research Institute of Nephrology, Zhengzhou University, Zhengzhou 450052, P.R. China.
Aging (Albany NY). 2023 Oct 11;15(19):10681-10704. doi: 10.18632/aging.205107.
Diabetic kidney disease (DKD) is a renal microvascular disease caused by hyperglycemia that involves metabolic remodeling, oxidative stress, inflammation, and other factors. The mechanism is complex and not fully unraveled. We performed an integrated single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) and single-cell RNA-sequencing (scRNA-seq) analyses of kidneys from db/db and db/m mice to identify differential open chromatin regions and gene expression, particularly in genes related to proximal tubular reabsorption and secretion. We identified 9,776 differentially expressed genes (DEGs) and 884 cell type-specific transcription factors (TFs) across 15 cell types. Glucose and lipid transporters, and TFs related to the circadian rhythm in the proximal tubules had significantly higher expression in db/db mice than in db/m mice (<0.01). Crosstalk between podocytes and tubular cells in the proximal tubules was enhanced, and renal inflammation, oxidative stress, and fibrosis pathways were activated in db/db mice. Western blotting and immunohistochemical staining results showed that expression in the urine and kidneys of DKD patients was higher than that in non-diabetic kidney disease (NDKD) controls. The revealed landscape of chromatin accessibility and transcriptional profiles in db/db mice provide insights into the pathological mechanism of DKD.
糖尿病肾病（DKD）是一种由高血糖引起的肾脏微血管疾病，涉及代谢重塑、氧化应激、炎症等多种因素。其发病机制复杂，尚未完全阐明。我们对 db/db 和 db/m 小鼠的肾脏进行了转座酶可及染色质（scATAC-seq）和单细胞 RNA 测序（scRNA-seq）的综合单细胞测序分析，以鉴定差异开放染色质区域和基因表达，特别是与近端肾小管重吸收和分泌相关的基因。我们在 15 种细胞类型中鉴定了 9776 个差异表达基因（DEGs）和 884 个细胞类型特异性转录因子（TFs）。葡萄糖和脂质转运蛋白，以及与近端肾小管昼夜节律相关的 TFs 在 db/db 小鼠中的表达明显高于 db/m 小鼠（<0.01）。足细胞与近端肾小管细胞之间的串扰增强，db/db 小鼠中肾脏炎症、氧化应激和纤维化途径被激活。Western blot 和免疫组化染色结果显示，DKD 患者尿液和肾脏中的表达高于非糖尿病肾病（NDKD）对照。db/db 小鼠中染色质可及性和转录谱的揭示为 DKD 的病理机制提供了深入了解。
