Evidence map›Paper›PMID 33907245›Full record

ArticleScientific reports2021

HDAC2 targeting stabilizes the CoREST complex in renal tubular cells and protects against renal ischemia/reperfusion injury.

David D Aufhauser, Paul Hernandez, Seth J Concors, Ciaran O'Brien, Zhonglin Wang, Douglas R Murken, Arabinda Samanta, Ulf H Beier, Lauren Krumeich, Tricia R Bhatti and 10 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
3.9field-weighted citation impact, top 7% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 28 citations in OpenAlex.

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  11. Fragile X Premutation: Medications, Therapy and Lifestyle Advice.Pharmacogenomics and personalized medicine · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 6 institutions in 1 country.

David D AufhauserDepartment of Surgery, University of Wisconsin, Madison, WI, USA.
Paul HernandezDepartment of Surgery, University of Pennsylvania, Philadelphia, PA, USA.
Seth J ConcorsDepartment of Surgery, University of Pennsylvania, Philadelphia, PA, USA.
Ciaran O'BrienDepartment of Surgery, University of Pennsylvania, Philadelphia, PA, USA.
Zhonglin WangDepartment of Surgery, University of Pennsylvania, Philadelphia, PA, USA.
Douglas R MurkenDepartment of Surgery, University of Pennsylvania, Philadelphia, PA, USA.
Arabinda SamantaDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Ulf H BeierDivision of Nephrology, Department of Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, PA, USA.
Lauren KrumeichDepartment of Surgery, University of Pennsylvania, Philadelphia, PA, USA.
Tricia R BhattiDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Yanfeng WangDepartment of Surgery, University of Pennsylvania, Philadelphia, PA, USA.
Guanghui GeDepartment of Surgery, University of Pennsylvania, Philadelphia, PA, USA.
Liqing WangDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Shayan CheraghlouSchool of Medicine, Yale University, New Haven, CT, USA.
Florence F WagnerStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Edward B HolsonStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Jay H KalinDivision of Genetics, Departments of Medicine and Biological Chemistry and Molecular Pharmacology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
Philip A ColeDivision of Genetics, Departments of Medicine and Biological Chemistry and Molecular Pharmacology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA.
Wayne W HancockDepartment of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Matthew H LevineDepartment of Surgery, University of Pennsylvania, Philadelphia, PA, USA. Matthew.Levine@pennmedicine.upenn.edu.
University of Pennsylvania · USChildren's Hospital of Philadelphia · USBrigham and Women's Hospital · USBroad Institute · USUniversity of Wisconsin–Madison · USYale University · US

Funding

Protein Acylation and Methylation Mechanisms_Administrative SupplementR37GM062437 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI COLE, PHILIP A · 2013 to 2022
$4.1M
Mechanisms &Inhibition of Histone AcetyltransferasesR01GM062437 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI COLE, PHILIP A · 2001 to 2012
$3.8M
Class IIa HDAC and MEF2 Targeting to Promote Foxp3+ Treg Cell FunctionsR01AI123241 · NIAID · CHILDREN'S HOSP OF PHILADELPHIA · PI HANCOCK, WAYNE WILLIAM · 2016 to 2020
$2.1M
HDAC2 Inhibition Mitigates Renal Ischemia Reperfusion InjuryR01DK106243 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI LEVINE, MATTHEW HOWARD · 2016 to 2020
$1.8M
Histone/Protein Deacetylase Inhibitors Minimize Renal Ischemia-Reperfusion InjuryK08DK092282 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI LEVINE, MATTHEW HOWARD · 2011 to 2015
$768k
NIAID NIH HHS R01 AI123241NIDDK NIH HHS K08 DK092282NIDDK NIH HHS R01 DK106243NIGMS NIH HHS R01 GM062437NIGMS NIH HHS R37 GM062437NIH HHS DK106243-01A1NIH HHS GM62437
6 · The paper itself

Abstract

Histone/protein deacetylases (HDAC) 1 and 2 are typically viewed as structurally and functionally similar enzymes present within various co-regulatory complexes. We tested differential effects of these isoforms in renal ischemia reperfusion injury (IRI) using inducible knockout mice and found no significant change in ischemic tolerance with HDAC1 deletion, but mitigation of ischemic injury with HDAC2 deletion. Restriction of HDAC2 deletion to the kidney via transplantation or PAX8-controlled proximal renal tubule-specific Cre resulted in renal IRI protection. Pharmacologic inhibition of HDAC2 increased histone acetylation in the kidney but did not extend renal protection. Protein analysis demonstrated increased HDAC1-associated CoREST protein in HDAC2-/- versus WT cells, suggesting that in the absence of HDAC2, increased CoREST complex occupancy of HDAC1 can stabilize this complex. In vivo administration of a CoREST inhibitor exacerbated renal injury in WT mice and eliminated the benefit of HDAC2 deletion. Gene expression analysis of endothelin showed decreased endothelin levels in HDAC2 deletion. These data demonstrate that contrasting effects of HDAC1 and 2 on CoREST complex stability within renal tubules can affect outcomes of renal IRI and implicate endothelin as a potential downstream mediator.

Indexed as

AnimalsCo-Repressor ProteinsEndothelinsEnzyme InhibitorsFemaleGene DeletionHistone Deacetylase 1Histone Deacetylase 2IsoenzymesKidney Tubules, ProximalMaleMiceMice, KnockoutReperfusion InjuryCo-Repressor ProteinsEndothelinsEnzyme InhibitorsHdac1 protein, mouseHdac2 protein, mouseHistone Deacetylase 1Histone Deacetylase 2IsoenzymesRcor2 protein, mouse

Identifiers

PMID33907245
PMCPMC8079686
OpenAlexW3157673366

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Registered trials

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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.