ArticleDrug design, development and therapy2019
Inhibition of Disruptor of Telomeric Silencing 1-Like Alleviated Renal Ischemia and Reperfusion Injury-Induced Fibrosis by Blocking PI3K/AKT-Mediated Oxidative Stress.
Article in Drug design, development and therapy, 2019. 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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17 citing papers in PubMed, 31 citations in OpenAlex.
- Tissue Fibrosis Decoded via Cellular Senescence: Mechanisms, Treatments, and Emerging Technologies.Aging and disease · 2025Review
- DOT1L protects against podocyte injury in diabetic kidney disease through phospholipase C-like 1.Cell communication and signaling : CCS · 2024Article
- Role of Histone Modifications in Kidney Fibrosis.Medicina (Kaunas, Lithuania) · 2024Review
- Shared Genetic Features of Psoriasis and Myocardial Infarction: Insights From a Weighted Gene Coexpression Network Analysis.Journal of the American Heart Association · 2024Article
- Gain-of-function mutations in the catalytic domain ofScience advances · 2023Article
- A novel role of DOT1L in kidney diseases.Molecular biology reports · 2023Review
- Somatic Cell Reprogramming for Nervous System Diseases: Techniques, Mechanisms, Potential Applications, and Challenges.Brain sciences · 2023Review
- Kidney fibrosis: from mechanisms to therapeutic medicines.Signal transduction and targeted therapy · 2023Review
- Cellular senescence of renal tubular epithelial cells in renal fibrosis.Frontiers in endocrinology · 2023Review
- Hypoxic mesenchymal stem cell-derived extracellular vesicles ameliorate renal fibrosis after ischemia-reperfusion injure by restoring CPT1A mediated fatty acid oxidation.Stem cell research & therapy · 2022Article
- Protein Methylation in Diabetic Kidney Disease.Frontiers in medicine · 2022Review
- The Role of Histone H3 Methylation in Acute Kidney Injury.Drug design, development and therapy · 2022Review
- The Role and Mechanism of Lysine Methyltransferase and Arginine Methyltransferase in Kidney Diseases.Frontiers in pharmacology · 2022Review
- Histone methyltransferase DOT1L mediates the TGF-β1/Smad3 signaling pathway through epigenetic modification of SYK in myocardial infarction.Human cell · 2022Article
- The Role of Cell Division Autoantigen 1 (CDA1) in Renal Fibrosis of Diabetic Nephropathy.BioMed research international · 2021Review
- Review
- Emodin Retarded Renal Fibrosis Through Regulating HGF and TGFβ-Smad Signaling Pathway.Drug design, development and therapy · 2020Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIschemia/reperfusion (I/R) injury is a major cause of acute kidney injury, usually occurs during renal surgeries, and may eventually lead to chronic kidney diseases. However, effective therapeutic targets for renal I/R injury remain limited. PURPOSE: In the present study, we investigated whether inhibition of disruptor of telomeric silencing 1-like (Dot1l) could alleviate renal I/R in vivo and in vitro, as well as the potential mechanisms involved in this process.
methodsSprague-Dawley rats were subjected to right renal ischemia for 45 mins and reperfusion for 0, 7, or 14 days with and without the Dot1l inhibitor EPZ004777. In addition, human renal proximal tubular epithelial cell line human kidney-2 cells were subjected to the hypoxia/reoxygenation (H/R) process (ie, 3 hrs hypoxia, 12 hrs and 24 hrs reoxygenation), with or without Dot1l inhibitor or genetic knockdown.
resultsInhibition of Dot1l through EPZ004777 or genetic knockdown reduced the expression of alpha-smooth muscle actin, vimentin, and fibronectin in I/R- and H/R-induced injury. Moreover, H/R-induced fibrosis depended on oxidative stress in vitro. In addition, I/R- and H/R-induced generation of reactive oxygen species (ROS) was attenuated by EPZ004777 or small interfering RNA for Dot1l. Furthermore, the elevation of ROS induced by Dot1l was regulated via phosphatidylinositol 3-kinase (PI3K) and serine-threonine protein kinase (AKT) phosphorylation in vivo and in vitro.
conclusionInhibition of Dot1l alleviated renal fibrosis by preventing the generation of ROS via the PI3K/AKT pathway. These results indicate that inhibitor of Dot1l could be a potential therapeutic target for renal I/R injury.
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