ArticleAntioxidants & redox signaling2016
Epigenetic Histone Modifications Involved in Profibrotic Gene Regulation by 12/15-Lipoxygenase and Its Oxidized Lipid Products in Diabetic Nephropathy.
Article in Antioxidants & redox signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 63 citations in OpenAlex.
- Metabolic Memory-Mediated Epigenetic Regulation of EMT in Diabetic Kidney Disease: Mechanisms and Therapeutic Implications.International journal of molecular sciences · 2026Review
- Post‑translational modifications in diabetic kidney disease (Review).International journal of molecular medicine · 2026Review
- Beyond hyperglycemia: histone modification-mediated epigenetic dysregulation in diabetic retinopathy and nephropathy.Diabetology & metabolic syndrome · 2026Review
- Fatty acid metabolism: opportunities and challenges of traditional Chinese medicine in the treatment of renal fibrosis.Chinese medicine · 2026Review
- Roles of different methylation modifications in cardiovascular disease.Frontiers of medicine · 2025Review
- Role of nuclear receptors, lipid metabolism, and mitochondrial function in the pathogenesis of diabetic kidney disease.American journal of physiology. Renal physiology · 2025Review
- Oxidative Stress: A Culprit in the Progression of Diabetic Kidney Disease.Antioxidants (Basel, Switzerland) · 2024Review
- Recent Advances in the Management of Diabetic Kidney Disease: Slowing Progression.International journal of molecular sciences · 2024Review
- Arachidonic acid metabolism as a therapeutic target in AKI-to-CKD transition.Frontiers in pharmacology · 2024Review
- Pathomechanisms of Diabetic Kidney Disease.Journal of clinical medicine · 2023Review
- Transcriptional co-activators: emerging roles in signaling pathways and potential therapeutic targets for diseases.Signal transduction and targeted therapy · 2023Review
- The Role of Histone Modifications in the Pathogenesis of Diabetic Kidney Disease.International journal of molecular sciences · 2023Review
- Tissue transglutaminase exacerbates renal fibrosis via alternative activation of monocyte-derived macrophages.Cell death & disease · 2023Article
- Ferroptosis: a new strategy for Chinese herbal medicine treatment of diabetic nephropathy.Frontiers in endocrinology · 2023Review
- Single-cell multiomics reveals the complexity of TGFβ signalling to chromatin in iPSC-derived kidney organoids.Communications biology · 2022Article
- Effects of Inflammatory Factor Expression Regulated by 12/15 Lipoxygenase on Obesity-Related Nephropathy.Nutrients · 2022Article
- Activation of the NLRP3 inflammasome by RAC1 mediates a new mechanism in diabetic nephropathy.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Article
- Redox signaling, mitochondrial metabolism, epigenetics and redox active phytochemicals.Free radical biology & medicine · 2022Review
- 15-Lipoxygenase worsens renal fibrosis, inflammation, and metabolism in a murine model of ureteral obstruction.American journal of physiology. Renal physiology · 2022Article
- Sodium Butyrate Attenuates Diabetic Kidney Disease Partially via Histone Butyrylation Modification.Mediators of inflammation · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
aimsEpigenetic mechanisms, including histone post-translational modifications and DNA methylation, are implicated in the pathogenesis of diabetic nephropathy (DN), but the mediators are not well known. Moreover, although dyslipidemia contributes to DN, epigenetic changes triggered by lipids are unclear. In diabetes, increased expression of 12/15-lipoxygenase (12/15-LO) enhances oxidized lipids such as 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE], which promote oxidant stress, glomerular and mesangial cell (MC) dysfunction, and fibrosis, and mediate the actions of profibrotic growth factors. We hypothesized that 12/15-LO and its oxidized lipid products can regulate epigenetic mechanisms mediating profibrotic gene expression related to DN.
results12(S)-HETE increased profibrotic gene expression and enrichment of permissive histone lysine modifications at their promoters in MCs. 12(S)-HETE also increased protein levels of SET7, a histone H3 lysine 4 methyltransferase, and promoted its nuclear translocation and enrichment at profibrotic gene promoters. Furthermore, SET7 (Setd7) gene silencing inhibited 12(S)-HETE-induced profibrotic gene expression. 12/15-LO (Alox15) gene silencing or genetic knockout inhibited transforming growth factor-β1 (TGF-β1)-induced expression of Setd7 and profibrotic genes and histone modifications in MCs. Furthermore, 12/15-LO knockout in mice ameliorated key features of DN and abrogated increases in renal SET7 and profibrotic genes. Additionally, 12/15-LO siRNAs in vivo blocked increases in renal SET7 and profibrotic genes in diabetic mice. INNOVATION AND
conclusionThese novel results demonstrate for the first time that 12/15-LO-derived oxidized lipids regulate histone modifications associated with profibrotic gene expression in MCs, and 12/15-LO can mediate similar actions of TGF-β1 and diabetes. Targeting 12/15-LO might be a useful strategy to inhibit key epigenetic mechanisms involved in DN.
Indexed as
Identifiers
What OpenQuestion holds
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.