ArticleAmerican journal of physiology. Renal physiology2019
Dynamic changes in histone deacetylases following kidney ischemia-reperfusion injury are critical for promoting proximal tubule proliferation.
Article in American journal of physiology. Renal physiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Fluid-electrolyte homeostasis requires histone deacetylase function.JCI insight · 2020Pooled it
- Zinc Signaling in Acute Kidney Injury.Cells · 2026Review
- Fibroblast histone deacetylase-1 promotes kidney interstitial fibrosis following ischemia-reperfusion injury.American journal of physiology. Renal physiology · 2026Article
- Histone deacetylases and their inhibitors in kidney diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Histone deacetylases: potential therapeutic targets in cisplatin-induced acute kidney injury.Annals of medicine · 2024Review
- Epigenetics of Hypertensive Nephropathy.Biomedicines · 2024Review
- Histone deacetylase expression following cisplatin-induced acute kidney injury in male and female mice.American journal of physiology. Renal physiology · 2024Article
- Comprehensive analysis of the endothelin system in the kidneys of mice, rats, and humans.Bioscience reports · 2024Article
- Review
- Genetic and Epigenetic Mechanisms Regulating Blood Pressure and Kidney Dysfunction.Hypertension (Dallas, Tex. : 1979) · 2024Review
- Validation of HDAC8 Inhibitors as Drug Discovery Starting Points to Treat Acute Kidney Injury.ACS pharmacology & translational science · 2022Article
- Depleted HDAC3 attenuates hyperuricemia-induced renal interstitial fibrosis via miR-19b-3p/SF3B3 axis.Cell cycle (Georgetown, Tex.) · 2022Article
- Kidney cell type-specific changes in the chromatin and transcriptome landscapes following epithelialPhysiological genomics · 2022Article
- Molecular mechanisms of histone deacetylases and inhibitors in renal fibrosis progression.Frontiers in molecular biosciences · 2022Review
- Correlation analysis between expression of histone deacetylase 6 and clinical parameters in IgA nephropathy patients.Renal failure · 2021Article
- UAB-UCSD O'Brien Center for Acute Kidney Injury Research.American journal of physiology. Renal physiology · 2021Review
- The Role and Mechanism of Histone Deacetylases in Acute Kidney Injury.Frontiers in pharmacology · 2021Review
- Class IIa HDAC inhibitor TMP195 alleviates lipopolysaccharide-induced acute kidney injury.American journal of physiology. Renal physiology · 2020Article
- Histone Deacetylases in Kidney Physiology and Acute Kidney Injury.Seminars in nephrology · 2020Review
- Early Programming of Adult Systemic Essential Hypertension.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Deranged histone deacetylase (HDAC) activity causes uncontrolled proliferation, inflammation, fibrosis, and organ damage. It is unclear whether deranged HDAC activity results in acute kidney injury in the renal hypoperfusion model of bilateral ischemia-reperfusion injury (IRI) and whether in vivo inhibition is an appropriate therapeutic approach to limit injury. Male mice were implanted with intraperitoneal osmotic minipumps containing vehicle, the class I HDAC inhibitor, MS275, or the pan-HDAC inhibitor, trichostatin A (TSA), 3 days before sham/bilateral IRI surgery. Kidney cortical samples were analyzed using histological, immunohistochemical, and Western blotting techniques. HDAC-dependent proliferation rate was measured in immortalized rat epithelial cells and primary mouse or human proximal tubule (PT) cells. There were dynamic changes in cortical HDAC localization and abundance following IRI including a fourfold increase in HDAC4 in the PT. HDAC inhibition resulted in a significantly higher plasma creatinine, increased kidney damage, but reduced interstitial fibrosis compared with vehicle-treated IRI mice. HDAC-inhibited mice had reduced interstitial α-smooth muscle actin, fibronectin expression, and Sirius red-positive area, suggesting that IRI activates HDAC-mediated fibrotic pathways. In vivo proliferation of the kidney epithelium was significantly reduced in TSA-treated, but not MS275-treated, IRI mice, suggesting class II HDACs mediate proliferation. Furthermore, HDAC4 activation increased proliferation of human and mouse PTs. Kidney HDACs are activated during IRI with isoform-specific expression patterns. Our data point to mechanisms whereby IRI activates HDACs resulting in fibrotic pathways but also activation of PT proliferation and repair pathways. This study demonstrates the need to develop isoform-selective HDAC inhibitors for the treatment of renal hypoperfusion-induced injury.
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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 Socratic graph.