ArticleJournal of the American Society of Nephrology : JASN2022
Serum Protein Exposure Activates a Core Regulatory Program Driving Human Proximal Tubule Injury.
Article in Journal of the American Society of Nephrology : JASN, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Hypoalbuminemia induces immunosuppression through disorder in macrophages and drives resistance to immune checkpoint inhibitors.Cancer immunology, immunotherapy : CII · 2026Article
- Effect of calcium oxalate microcrystals on kidney proximal tubule epithelial cell gene expression in microgravity.NPJ microgravity · 2025Article
- BCKDK accelerates the progression of diabetic kidney disease by regulating leucine-mediated metabolic remodelling in renal tubular cells.Diabetologia · 2025Article
- Proteinuria as an End Point in Clinical Trials of Focal Segmental Glomerulosclerosis.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2025Review
- Nephrotic syndrome induces the upregulation of cell proliferation-related genes in tubular cells in mice.Clinical and experimental nephrology · 2025Article
- Protein handling in kidney tubules.Nature reviews. Nephrology · 2025Review
- Crosstalk between glomeruli and tubules.Nature reviews. Nephrology · 2025Review
- A guide to studying 3D genome structure and dynamics in the kidney.Nature reviews. Nephrology · 2025Review
- Comparative analysis of the physiological and transport functions of various sources of renal proximal tubule cells under static and fluidic conditions in PhysioMimix T12 platform.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Modeling cellular responses to serum and vitamin D in microgravity using a human kidney microphysiological system.NPJ microgravity · 2024Article
- Development of a kidney microphysiological system hardware platform for microgravity studies.NPJ microgravity · 2024Article
- Multi-omic analysis of human kidney tissue identified medulla-specific gene expression patterns.Kidney international · 2024Article
- Development of a Kidney Microphysiological System Hardware Platform for Microgravity Studies.Research square · 2023Article
- Impact of microgravity on a three-dimensional microphysiologic culture of the human kidney proximal tubule epithelium: cell response to serum and vitamin D.Research square · 2023Article
- Is Albumin Toxic to the Kidney?: It Depends.Clinical journal of the American Society of Nephrology : CJASN · 2023Article
- Emerging roles of proximal tubular endocytosis in renal fibrosis.Frontiers in cell and developmental biology · 2023Review
- Chromatin accessibility dynamics dictate renal tubular epithelial cell response to injury.Nature communications · 2022Article
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13 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe kidneys efficiently filter waste products while retaining serum proteins in the circulation. However, numerous diseases compromise this barrier function, resulting in spillage of serum proteins into the urine (proteinuria). Some studies of glomerular filtration suggest that tubules may be physiologically exposed to nephrotic-range protein levels. Therefore, whether serum components can directly injure the downstream tubular portions of the kidney, which in turn can lead to inflammation and fibrosis, remains controversial.
methodsWe tested the effects of serum protein exposure in human kidney tubule microphysiologic systems and with orthogonal epigenomic approaches since animal models cannot directly assess the effect of serum components on tubules.
resultsSerum, but not its major protein component albumin, induced tubular injury and secretion of proinflammatory cytokines. Epigenomic comparison of serum-injured tubules and intact kidney tissue revealed canonical stress-inducible regulation of injury-induced genes. Concordant transcriptional changes in microdissected tubulointerstitium were also observed in an independent cohort of patients with proteinuric kidney disease.
conclusionsOur results demonstrate a causal role for serum proteins in tubular injury and identify regulatory mechanisms and novel pathways for intervention.
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