ArticleJCI insight2021
Loss of diacylglycerol kinase ε causes thrombotic microangiopathy by impairing endothelial VEGFA signaling.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 22 citations in OpenAlex.
- IPNA clinical practice recommendations for the management of aHUS and secondary TMA in children.Pediatric nephrology (Berlin, Germany) · 2026Article
- Thrombotic microangiopathy after kidney transplantation: diagnosis and management strategies.Clinical kidney journal · 2026Review
- Modulators of Diacylglycerol Kinase Activity: A Review of Advances and Challenges.Medicinal research reviews · 2026Review
- DGKs in lipid signaling and disease intervention: structural basis, pathological mechanisms, and emerging therapeutic strategies.Cellular & molecular biology letters · 2025Review
- Post-transplant Thrombotic Microangiopathy.Journal of the American Society of Nephrology : JASN · 2025Review
- Renal microcirculation and mechanisms in diabetic kidney disease.Frontiers in endocrinology · 2025Review
- RNA Sequencing Revealed a Weak Response of Gingival Fibroblasts Exposed to Hyaluronic Acid.Bioengineering (Basel, Switzerland) · 2024Article
- Diacylglycerol Kinases and Its Role in Lipid Metabolism and Related Diseases.International journal of molecular sciences · 2024Review
- Maternal exposure to polystyrene nanoplastics induces sex-specific cardiotoxicity in offspring mice.Heliyon · 2024Article
- Dysregulation of Immune Cell Subpopulations in Atypical Hemolytic Uremic Syndrome.International journal of molecular sciences · 2023Article
- Clinical features and management of atypical hemolytic uremic syndrome patient withFrontiers in pediatrics · 2023Review
- Diagnosis and treatment of thrombotic microangiopathy.International journal of laboratory hematology · 2022Review
- The Glomerular Endothelium Restricts Albumin Filtration.Frontiers in medicine · 2021Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Loss of function of the lipid kinase diacylglycerol kinase ε (DGKε), encoded by the gene DGKE, causes a form of atypical hemolytic uremic syndrome that is not related to abnormalities of the alternative pathway of the complement, by mechanisms that are not understood. By generating a potentially novel endothelial specific Dgke-knockout mouse, we demonstrate that loss of Dgke in the endothelium results in impaired signaling downstream of VEGFR2 due to cellular shortage of phosphatidylinositol 4,5-biphosphate. Mechanistically, we found that, in the absence of DGKε in the endothelium, Akt fails to be activated upon VEGFR2 stimulation, resulting in defective induction of the enzyme cyclooxygenase 2 and production of prostaglandin E2 (PGE2). Treating the endothelial specific Dgke-knockout mice with a stable PGE2 analog was sufficient to reverse the clinical manifestations of thrombotic microangiopathy and proteinuria, possibly by suppressing the expression of matrix metalloproteinase 2 through PGE2-dependent upregulation of the chemokine receptor CXCR4. Our study reveals a complex array of autocrine signaling events downstream of VEGFR2 that are mediated by PGE2, that control endothelial activation and thrombogenic state, and that result in abnormalities of the glomerular filtration barrier.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.