Exploring the pathogenesis of diabetic kidney disease by microarray data analysis

Cao, Haiyan; Rao, Xiaosheng; Jia, Junya; Yan, Tiekun; Liu, Dong

doi:10.3389/fphar.2022.932205

Cited by 6 publications

(7 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A DEG analysis revealed that more than half of the genes (∼15k) were significantly differentially expressed (p < 0.05; Student’s t-test with Benjamini-Hochberg correction [29]). This uncommonly high number of DEGs, which is typically on the order of a few hundred in studies of blood samples from patients with other diseases, such as coronary artery disease [30], obesity [31, 32], diabetes [33, 34] or kidney [35], led us to hypothesize that the observed variability might arise from cellular heterogeneity across synovial biopsies, rather than from intra-cellular gene expression differences between the two tested groups. To test this hypothesis, we used xCell [36] to estimate the relative proportions of the various cell populations present in our samples.…”

Section: Resultsmentioning

confidence: 99%

Cell-Specific Gene Networks and Drivers in Rheumatoid Arthritis Synovial Tissues

Pelissier,

Laragione,

Gulko

et al. 2023

Preprint

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is a common autoimmune and inflammatory disease characterized by inflammation and hyperplasia of the synovial tissues. RA pathogenesis involves multiple cell types, genes, transcription factors (TFs) and networks. Yet, little is known about the TFs, and key drivers and networks regulating cell function and disease at the synovial tissue level, which is the site of disease. In the present study, we used available RNA-seq databases generated from synovial tissues and developed a novel approach to elucidate cell type-specific regulatory networks on synovial tissue genes in RA. We leverage established computational methodologies to infer sample-specific gene regulatory networks and applied statistical methods to compare network properties across phenotypic groups (RA versus osteoarthritis). We developed computational approaches to rank TFs based on their contribution to the observed phenotypic differences between RA and controls across different cell types. We identified 18,16,19,11 key regulators of fibroblast-like synoviocyte (FLS), T cells, B cells, and monocyte signatures and networks, respectively, in RA synovial tissues. Interestingly, FLS and B cells were driven by multiple independent co-regulatory TF clusters that included MITF, HLX, BACH1 (FLS) and KLF13, FOSB, FOSL1 (synovial B cells). However, monocytes were collectively governed by a single cluster of TF drivers, responsible for the main phenotypic differences between RA and controls, which included RFX5, IRF9, CREB5. Among several cell subset and pathway changes, we also detected reduced presence of NKT cell and eosinophils in RA synovial tissues. Overall, our novel approach identified new and previously unsuspected KDG, TF and networks and should help better understanding individual cell regulation and co-regulatory networks in RA pathogenesis, as well as potentially generate new targets for treatment.

show abstract

Section: Resultsmentioning

confidence: 99%

Cell-Specific Gene Networks and Drivers in Rheumatoid Arthritis Synovial Tissues

Pelissier,

Laragione,

Gulko

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…A recent study has revealed that albuminuria can activate the Wnt/β-catenin signaling pathway in renal TECs, promoting the expression of TLR4/NLRP3-associated chemokines and inflammatory factors, thereby causing renal tubular and tubulointerstitial inflammation ( 57 ). Microarray data analysis has revealed the important role of inflammation-related signaling pathways in the pathogenesis of both glomerular and tubular DKD ( 58 ). The TECs of patients with DKD are affected by the inflammatory response, resulting in excessive production of intracellular inflammatory mediators which further activate apoptosis, glycolysis, and apoptosis-related pathways and induce renal tubular injury.…”

Section: Mechanismmentioning

confidence: 99%

Tubular injury in diabetic kidney disease: molecular mechanisms and potential therapeutic perspectives

et al. 2023

View full text Add to dashboard Cite

Diabetic kidney disease (DKD) is a chronic complication of diabetes and the leading cause of end-stage renal disease (ESRD) worldwide. Currently, there are limited therapeutic drugs available for DKD. While previous research has primarily focused on glomerular injury, recent studies have increasingly emphasized the role of renal tubular injury in the pathogenesis of DKD. Various factors, including hyperglycemia, lipid accumulation, oxidative stress, hypoxia, RAAS, ER stress, inflammation, EMT and programmed cell death, have been shown to induce renal tubular injury and contribute to the progression of DKD. Additionally, traditional hypoglycemic drugs, anti-inflammation therapies, anti-senescence therapies, mineralocorticoid receptor antagonists, and stem cell therapies have demonstrated their potential to alleviate renal tubular injury in DKD. This review will provide insights into the latest research on the mechanisms and treatments of renal tubular injury in DKD.

show abstract

“…In the past, renal impairment due to diabetes mellitus was predominantly a condition that was first preceded by albuminuria and then followed by a decrease in eGFR ( 1 , 2 ). Recently, however, a decrease in glomerular filtration rate (GFR) without obvious albuminuria has been observed.…”

mentioning

confidence: 99%

“…Recently, however, a decrease in glomerular filtration rate (GFR) without obvious albuminuria has been observed. Therefore, the concept of diabetic kidney disease has been proposed as an umbrella concept for diabetic nephropathy ( 1 , 2 ). In recent years, improvements in renal prognosis with SGLT2 inhibitors and GLP-1 receptor agonists have been reported, and the effects of these drugs are actually felt in clinical practice ( 3 ), but the pathogenesis of DKD still remains largely unexplored.…”

mentioning

confidence: 99%

“…The mechanisms of glomerular and tubulointerstitial injury in diabetic kidney disease are different, but there are many intersections of the related pathways and mediators. Furthermore, proximal tubular injury has an important role in the progression of diabetic kidney disease with/without proteinuria ( 2 , 4 ). Therefore, in this volume, some papers focused on renal tubular epithelial cells.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Editorial: Advances in the research of diabetic nephropathy, volume II

et al. 2023

View full text Add to dashboard Cite

Editroial on the Research TopicAdvances in the research of diabetic nephropathy volume II In the past, renal impairment due to diabetes mellitus was predominantly a condition that was first preceded by albuminuria and then followed by a decrease in eGFR (1, 2). Recently, however, a decrease in glomerular filtration rate (GFR) without obvious albuminuria has been observed. Therefore, the concept of diabetic kidney disease has been proposed as an umbrella concept for diabetic nephropathy (1, 2). In recent years, improvements in renal prognosis with SGLT2 inhibitors and GLP-1 receptor agonists have been reported, and the effects of these drugs are actually felt in clinical practice (3), but the pathogenesis of DKD still remains largely unexplored.Recently, the role of proximal renal tubule cells in the pathogenesis of diabetic kidney disease has been the focus of research (4). Diabetic glomerulonephropathy is mainly injury to glomeruli. In contrast, diabetic kidney disease involves not only renal glomerulonephropathy but also tubulointerstitial fibrosis. Based on the anatomically distinct regions of kidney biopsy samples, diabetic kidney disease can be divided into glomerular diabetic kidney disease and tubular diabetic kidney disease. The common characteristics of glomerular diabetic kidney disease involve a damaged glomerular filtration barrier, mesangial cell proliferation, and glomerulosclerosis. The major manifestations of tubular diabetic kidney disease include dysfunction of renal tubular reabsorption and secretion and tubulointerstitial fibrosis (4). The mechanisms of glomerular and tubulointerstitial injury in diabetic kidney disease are different, but there are many intersections of the related pathways and mediators. Furthermore, proximal tubular injury has an important role in the progression of diabetic kidney disease with/without proteinuria (2, 4). Therefore, in this volume, some papers focused on renal tubular epithelial cells.The cilium is a microtubule-based organelle that projects from the surface of most vertebrate cell types and detects and transmits extracellular signals ( 5). The ciliary life cycle is also closely related to the cell cycle. Renal primary cilia are sensory antennas required for the Frontiers in Endocrinology frontiersin.org 01

show abstract

Exploring the pathogenesis of diabetic kidney disease by microarray data analysis

Cited by 6 publications

References 69 publications

Cell-Specific Gene Networks and Drivers in Rheumatoid Arthritis Synovial Tissues

Cell-Specific Gene Networks and Drivers in Rheumatoid Arthritis Synovial Tissues

Tubular injury in diabetic kidney disease: molecular mechanisms and potential therapeutic perspectives

Editorial: Advances in the research of diabetic nephropathy, volume II

Contact Info

Product

Resources

About