Dynamic changes in histone deacetylases following kidney ischemia-reperfusion injury are critical for promoting proximal tubule proliferation

American Journal of Physiology. Renal Physiology
Kelly A HyndmanSureena Monteiro-Pai

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 a...Continue Reading

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Citations

Jul 4, 2019·American Journal of Physiology. Renal Physiology·Timothy D HewitsonEdward R Smith
Feb 15, 2020·International Journal of Molecular Sciences·Verónica Guarner-LansIsrael Pérez-Torres
Jul 17, 2020·JCI Insight·Kelly A HyndmanJennifer S Pollock
Oct 6, 2020·American Journal of Physiology. Renal Physiology·Wei ZhangShougang Zhuang
Apr 19, 2020·Seminars in Nephrology·Kelly A Hyndman
Mar 30, 2021·American Journal of Physiology. Renal Physiology·Lisa M CurtisAnupam Agarwal
May 7, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Bassant M El-MokademAyman A Soubh
Jul 6, 2021·Frontiers in Pharmacology·Xun ZhouNa Liu

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Datasets Mentioned

BETA
AB111318

Methods Mentioned

BETA
RNA-Seq
PCR
transfection
acetylation
ubiquitination

Software Mentioned

PrimerBank
Fiji
ImageJ

Related Concepts

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