Effect of TNFα stimulation on expression of kidney risk inflammatory proteins in human umbilical vein endothelial cells cultured in hyperglycemia
Open accessAbstract
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 TNFα. In this in vitro study, we examined intracellular and extracellular levels of these proteins in human umbilical vein endothelial cells (HUVECs) exposed to TNFα 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 TNFα-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 TNFα. 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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The SomaLogic aptamer-based platform can reliably quantify over 7,000 proteins in a variety of biofluids and cellular extracts.
“Although the SomaLogic aptamer-based platform is especially powerful and can reliably quantify over 7,000 proteins in a variety of biofluids and cellular extracts103–106, it is not yet possible to reliably quantify the entire proteome.”
From Measuring biological age using omics data (2022) · cites this paper as [104]
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Measuring biological age using omics data
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Comparative analysis of pathways induced by TMAO and TNF-α in human microvascular endothelial cells
Shanmugham, M., Devasia, A. G., Oguz, G., Ramasamy, A., Lim, Z. Z. Y., Bellanger, S., & Leo, C. H. (2026) · Scientific Reports · doi:10.1038/s41598-026-46466-1 · Cited by 1 · see citing works
- Authors
- Md Dom, Z. I., Pipino, C., Krolewski, B., O’Neil, K., Satake, E., & Krolewski, A. S.
- Affiliations
- Joslin Diabetes Center (US)
- Venue
- Scientific Reports
- Published
- 2021-05-27
- Volume
- 11
- Issue
- 1
- Pages
- 11133-11133
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC8160214
- OpenAlex
- W3165367973
- Cited by
- 4
- References
- 46
- Citations by year
- 2026: 1 · 2025: 1 · 2022: 2
- FWCI
- 0.34
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- The Sunstar Foundation
- Foundation for Growth Science Japan
- JDRF (17-2013-311)
- National Institutes of Health (DK041526-27)
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- TNF-α, hyperglycemia, human umbilical vein endothelial cells, TNF receptor 1, TNF receptor 2, IL18R1, CCL14, end-stage renal disease, diabetic nephropathy, inflammation, endothelial cells, proteomics
- MeSH terms
- Fibroblasts, Humans, Hyperglycemia, Inflammation, Tumor Necrosis Factor-alpha, Down-Regulation, Up-Regulation, Receptors, Tumor Necrosis Factor, Human Umbilical Vein Endothelial Cells
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