Coagulation, protease-activated receptors, and diabetic kidney disease: Lessons from enos-deficient mice

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Abstract

Endothelial nitric oxide synthase (eNOS) dysfunction is known to exacerbate the progression and prognosis of diabetic kidney disease (DKD). One of the mechanisms through which this is achieved is that low eNOS levels are associated with hypercoagulability, which promotes kidney injury. In the extrinsic coagulation cascade, the tissue factor (factor III) and downstream coagulation factors, such as active factor X (FXa), exacerbate inflammation through activation of the protease-activated receptors (PARs). Recently, it has been shown that the lack of or reduced eNOS expression in diabetic mice, as a model of advanced DKD, increases renal tissue factor levels and PAR1 and 2 expression in their kidneys. Furthermore, pharmaceutical inhibition or genetic deletion of coagulation factors or PARs ameliorated inflammation in DKD in mice lacking eNOS. In this review, we summarize the relationship between eNOS, coagulation, and PARs and propose a novel therapeutic option for the management of patients with DKD.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalTohoku Journal of Experimental Medicine
Volume255
Issue number1
DOIs
Publication statusPublished - 2021

Keywords

  • Diabetic glomerulosclerosis
  • Factor Xa
  • Inflammation
  • Tissue factor

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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