Glomerular Endothelial Cells as Instigators of Glomerular Sclerotic Diseases

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Abstract

Glomerular endothelial cell (GEnC) dysfunction is important in the pathogenesis of glomerular sclerotic diseases, including Focal Segmental Glomerulosclerosis (FSGS) and overt diabetic nephropathy (DN). GEnCs form the first cellular barrier in direct contact with cells and factors circulating in the blood. Disturbances in these circulating factors can induce GEnC dysfunction. GEnC dysfunction occurs in early stages of FSGS and DN, and is characterized by a compromised endothelial glycocalyx, an inflammatory phenotype, mitochondrial damage and oxidative stress, aberrant cell signaling, and endothelial-to-mesenchymal transition (EndMT). GEnCs are in an interdependent relationship with podocytes and mesangial cells, which involves bidirectional cross-talkviaintercellular signaling. Given that GEnC behavior directly influences podocyte function, it is conceivable that GEnC dysfunction may culminate in podocyte damage, proteinuria, subsequent mesangial activation, and ultimately glomerulosclerosis. Indeed, GEnC dysfunction is sufficient to cause podocyte injury, proteinuria and activation of mesangial cells. Aberrant gene expression patterns largely contribute to GEnC dysfunction and epigenetic changes seem to be involved in causing aberrant transcription. This review summarizes literature that uncovers the importance of cross-talk between GEnCs and podocytes, and GEnCs and mesangial cells in the context of the development of FSGS and DN, and the potential use of GEnCs as efficacious cellular target to pharmacologically halt development and progression of DN and FSGS.

Original languageEnglish
Article number573557
Number of pages13
JournalFrontiers in Pharmacology
Volume11
DOIs
Publication statusPublished - 6-Oct-2020

Keywords

  • Kidney glomerulus (MeSH
  • D007678)
  • Glycocalyx (MeSH
  • D019276)
  • Endothelial cells (MeSH
  • D042783)
  • Podocytes (MeSH
  • D050199)
  • Proteinuria (MeSH
  • D011507)
  • Diabetic Nephropathy (MeSH
  • D003928)
  • Focal Segmental Glomerulosclerosis (MeSH
  • D005923)
  • TO-MESENCHYMAL TRANSITION
  • FOCAL SEGMENTAL GLOMERULOSCLEROSIS
  • NITRIC-OXIDE SYNTHASE
  • ZESTE HOMOLOG 2
  • DIABETIC-NEPHROPATHY
  • KIDNEY-DISEASE
  • GENE-EXPRESSION
  • ADVANCED GLYCATION
  • OXIDATIVE STRESS
  • RENAL FIBROSIS

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