Extracellular Vesicles in Renal Diseases

Erdbrügger, Uta; Le, Thu H.

doi:10.1681/asn.2015010074

Cited by 165 publications

(183 citation statements)

References 125 publications

Supporting

Mentioning

175

Contrasting

Unclassified

Order By: Relevance

“…In addition, extracellular vesicles including exosomes and microparticles (MPs) are emerging as novel vectors for cell–cell communication [12,13]. MPs are small plasma membrane-derived vesicles with a diameter of 100–1000 nm which carry a variety of proteins, lipids, mRNA and miRNA arising from the cell of origin [13,14].…”

Section: Introductionmentioning

confidence: 99%

Podocyte‐derived microparticles promote proximal tubule fibrotic signaling via p38 MAPK and CD36

Munkonda

Akbari

Landry

et al. 2018

J of Extracellular Vesicle

View full text Add to dashboard Cite

Tubulointerstitial fibrosis is a hallmark of advanced diabetic kidney disease that is linked to a decline in renal function, however the pathogenic mechanisms are poorly understood. Microparticles (MPs) are 100–1000 nm vesicles shed from injured cells that are implicated in intercellular signalling. Our lab recently observed the formation of MPs from podocytes and their release into urine of animal models of type 1 and 2 diabetes and in humans with type 1 diabetes. The purpose of the present study was to examine the role of podocyte MPs in tubular epithelial cell fibrotic responses. MPs were isolated from the media of differentiated, untreated human podocytes (hPODs) and administered to cultured human proximal tubule epithelial cells (PTECs). Treatment with podocyte MPs increased p38 and Smad3 phosphorylation and expression of the extracellular matrix (ECM) proteins fibronectin and collagen type IV. MP-induced responses were attenuated by co-treatment with the p38 inhibitor SB202190. A transforming growth factor beta (TGF-β) receptor inhibitor (LY2109761) blocked MP-induced Smad3 phosphorylation and ECM protein expression but not p38 phosphorylation suggesting that these responses occurred downstream of p38. Finally, blockade of the class B scavenger receptor CD36 completely abrogated MP-mediated p38 phosphorylation, downstream Smad3 activation and fibronectin/collagen type IV induction. Taken together our results suggest that podocyte MPs interact with proximal tubule cells and induce pro-fibrotic responses. Such interactions may contribute to the development of tubular fibrosis in glomerular disease.

show abstract

Section: Introductionmentioning

confidence: 99%

Podocyte‐derived microparticles promote proximal tubule fibrotic signaling via p38 MAPK and CD36

Munkonda

Akbari

Landry

et al. 2018

J of Extracellular Vesicle

View full text Add to dashboard Cite

show abstract

“…Exosomes are a type of extracellular vesicles 30–100 nm in diameter that play a pivotal role in cell– cell communication [18]. Emerging studies have shown that exosomes act as key regulators of kidney injury [19]. Our previous studies have also found that transcriptomic changes in urinary exosomes can be utilized as discriminative biomarkers of mild renal fibrosis [20, 21], indicating their potential roles as the regulators and biomarkers of kidney injury.…”

Section: Discussionmentioning

confidence: 99%

Integrative Bioinformatics Analysis Provides Insight into the Molecular Mechanisms of Chronic Kidney Disease

Zhou

Qiu

et al. 2018

Kidney Blood Press Res

View full text Add to dashboard Cite

Background/Aims: Chronic kidney disease (CKD) is a worldwide public health problem. Regardless of the underlying primary disease, CKD tends to progress to end-stage kidney disease, resulting in unsatisfactory and costly treatment. Its common pathogenesis, however, remains unclear. The aim of this study was to provide an unbiased catalog of common gene-expression changes of CKD and reveal the underlying molecular mechanism using an integrative bioinformatics approach. Methods: We systematically collected over 250 Affymetrix microarray datasets from the glomerular and tubulointerstitial compartments of healthy renal tissues and those with various types of established CKD (diabetic kidney disease, hypertensive nephropathy, and glomerular nephropathy). Then, using stringent bioinformatics analysis, shared differentially expressed genes (DEGs) of CKD were obtained. These shared DEGs were further analyzed by the gene ontology (GO) and pathway enrichment analysis. Finally, the protein-protein interaction networks(PINs) were constructed to further refine our results. Results: Our analysis identified 176 and 50 shared DEGs in diseased glomeruli and tubules, respectively, including many transcripts that have not been previously reported to be involved in kidney disease. Enrichment analysis also showed that the glomerular and tubulointerstitial compartments underwent a wide range of unique pathological changes during chronic injury. As revealed by the GO enrichment analysis, shared DEGs in glomeruli were significantly enriched in exosomes. By constructing PINs, we identified several hub genes (e.g. OAS1, JUN, and FOS) and clusters that might play key roles in regulating the development of CKD. Conclusion: Our study not only further reveals the unifying molecular mechanism of CKD pathogenesis but also provides a valuable resource of potential biomarkers and therapeutic targets.

show abstract

“…It is crucial that researchers provide detailed information about their methodology and use several techniques to ensure that the particles that they are studying are truly EVs and not non-EV components, such as lipids or protein complexes. In addition, a standard and uniform language should be used among all scientific communications [74].…”

Section: Microparticles In Kidney Transplantationmentioning

confidence: 99%