Abstract
The prevalence of diabetes is consistently rising worldwide. Diabetic nephropathy is a leading cause of chronic renal failure. The present study aimed to explore the crosstalk among the different cell types inside diabetic glomeruli, including glomerular endothelial cells, mesangial cells, podocytes, and immune cells, by analyzing an online single-cell RNA profile (GSE131882) of patients with diabetic nephropathy. Differentially expressed genes in the glomeruli were processed by gene enrichment and protein-protein interactions analysis. Glomerular endothelial cells, as well as podocytes, play a critical role in diabetic nephropathy. A subgroup of glomerular endothelial cells possesses characteristic angiogenesis genes, indicating that angiogenesis takes place in the progress of diabetic nephropathy. Immune cells such as macrophages, T lymphocytes, B lymphocytes, and plasma cells also contribute to the disease progression. By using iTALK, the present study reports complicated cellular crosstalk inside glomeruli. Dysfunction of glomerular endothelial cells and immature angiogenesis result from the activation of both paracrine and autocrine signals. The present study reinforces the importance of glomerular endothelial cells in the development of diabetic nephropathy. The exploration of the signaling pathways involved in aberrant angiogenesis reported in the present study shed light on potential therapeutic target(s) for diabetic nephropathy.
Highlights
The prevalence of diabetes keeps rising worldwide [1]
By performing bioinformatics analysis on the online singlenucleus RNA sequencing dataset regarding glomerular cells in diabetic patients [28], the present study reports that [1] glomerular endothelial cells play a critical role in the development of diabetic nephropathy; [2] apart from wellstudied diabetes/high glucose-induced endothelial dysfunction, a group of glomerular endothelial cells possesses characteristic angiogenesis genes; and [3] immune cells such as macrophages, T lymphocytes, B lymphocytes, and plasma cells take part in the progress of diabetic nephropathy
It is reported that podocyte counts increase in the early stage and decrease in the advanced stage of diabetes [42, 43]
Summary
The prevalence of diabetes keeps rising worldwide [1]. Diabetes and diabetes-induced complications remarkably affect life quality and reduce life span compared with the non-diabetes population, many advances have been made in the early diagnosis and clinical treatments [1, 2]. Diabetes-induced complications include retinopathy, nephropathy, and neuropathy. Diabetic nephropathy is a leading cause of chronic renal failure. Patients with diabetic nephropathy present albuminuria (
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