4.7 Article

Effect of TNFα stimulation on expression of kidney risk inflammatory proteins in human umbilical vein endothelial cells cultured in hyperglycemia

Journal

SCIENTIFIC REPORTS
Volume 11, Issue 1, Pages -

Publisher

NATURE RESEARCH
DOI: 10.1038/s41598-021-90496-w

Keywords

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Funding

  1. JDRF [17-2013-311]
  2. National Institutes of Health [DK041526-27]
  3. Sunstar Foundation (Hiroo Kaneda Scholarship)
  4. Foundation for Growth Science from Japan
  5. NIH Diabetes Research Center (DRC) [P30 DK36836]

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The study identified a kidney risk inflammatory signature (KRIS) consisting of 6 TNF receptors and 11 inflammatory proteins, which were found to be strongly associated with end-stage kidney disease (ESKD). In vitro experiments showed that TNF alpha stimulation affected the expression of KRIS proteins in human umbilical vein endothelial cells (HUVECs), while exposure to a hyperglycemic and inflammatory environment led to up-regulation of a distinct set of proteins.
We recently identified a kidney risk inflammatory signature (KRIS), comprising 6 TNF receptors (including TNFR1 and TNFR2) and 11 inflammatory proteins. Elevated levels of these proteins in circulation were strongly associated with risk of the development of end-stage kidney disease (ESKD) during 10-year follow-up. It has been hypothesized that elevated levels of these proteins in circulation might reflect (be markers of) systemic exposure to TNF alpha. In this in vitro study, we examined intracellular and extracellular levels of these proteins in human umbilical vein endothelial cells (HUVECs) exposed to TNF alpha in the presence of hyperglycemia. KRIS proteins as well as 1300 other proteins were measured using the SOMAscan proteomics platform. Four KRIS proteins (including TNFR1) were down-regulated and only 1 protein (IL18R1) was up-regulated in the extracellular fraction of TNF alpha -stimulated HUVECs. In the intracellular fraction, one KRIS protein was down-regulated (CCL14) and 1 protein was up-regulated (IL18R1). The levels of other KRIS proteins were not affected by exposure to TNF alpha. HUVECs exposed to a hyperglycemic and inflammatory environment also showed significant up-regulation of a distinct set of 53 proteins (mainly in extracellular fraction). In our previous study, circulating levels of these proteins were not associated with progression to ESKD in diabetes.

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