PXD016731

PXD016731 is an original dataset announced via ProteomeXchange.

Title	Rhein, a novel Histone Deacetylase (HDAC) inhibitor with antifibrotic potency in human myocardial fibrosis
Description	Although fibrosis depicts a reparative mechanism, maladaptation of the heart due to excessive production of extracellular matrix accelerates cardiac dysfunction. The anthraquinone Rhein was examined for its anti-fibrotic potency to mitigate cardiac fibroblast-to-myofibroblast transition (FMT). Primary human ventricular cardiac fibroblasts were subjected to hypoxia and characterized with proteomics, transcriptomics and cell functional techniques. Knowledge based analyses of the omics data revealed a modulation of fibrosis-associated pathways and cell cycle due to Rhein administration during hypoxia, whereas p53 and p21 were identified as upstream regulators involved in the manifestation of cardiac fibroblast phenotypes. Mechanistically, Rhein-mediated cellular effects were linked to the histone deacetylase (HDAC)-dependent acetylation status of p53 a posttranslational modification that acts protein stabilizing. Direct enzymatic testing revealed an inhibitory potency of Rhein for HDAC classes I/II. Functionally, Rhein inhibited collagen contraction in response to protein abundance of SMAD7, thus demonstrating its anti-fibrotic property in cardiac remodeling. In conclusion, this study identifies Rhein as a novel potent HDAC inhibitor and provides evidence that Rhein may contribute to the treatment of cardiac fibrosis as anti-fibrotic agent. As readily available drug with approved safety, repurposing of Rhein constitutes a promising potential therapeutic approach in the supplemental and protective intervention of cardiac fibrosis.
HostingRepository	PRIDE
AnnounceDate	2020-03-23
AnnouncementXML	Submission_2020-03-22_23:43:37.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Birgit Knebel
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2019-12-13 00:13:49	ID requested
⏵ 1	2020-03-22 23:43:38	announced

Barbosa DM, Fahlbusch P, Herzfeld de Wiza D, Jacob S, Kettel U, Al-Hasani H, Kr, ü, ger M, Ouwens DM, Hartwig S, Lehr S, Kotzka J, Knebel B, Rhein, a novel Histone Deacetylase (HDAC) inhibitor with antifibrotic potency in human myocardial fibrosis. Sci Rep, 10(1):4888(2020) [pubmed]

curator keyword: Biomedical

submitter keyword: Cardiac remodeling, fibrosis, HDAC inhibition, hypoxia, secretome, Lumos, DIA, Spectronaut

Birgit Knebel
contact affiliation	Dr. rer. nat. Birgit Knebel Institute for Clinical Biochemistry and Pathobiochemistry German Diabetes Center (DDZ) Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf Auf´m Hennekamp 65 40225 Düsseldorf, Germany
contact email	Birgit.Knebel@DDZ.de
lab head
Birgit Knebel
contact affiliation	Institute for Clinical Biochemistry and Pathobiochemistry German Diabetes Center (DDZ) Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf
contact email	birgit.knebel@ddz.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/03/PXD016731

PRIDE project URI

• PRIDE
  1. PXD016731
     1. Label: PRIDE project
     2. Name: Rhein, a novel Histone Deacetylase (HDAC) inhibitor with antifibrotic potency in human myocardial fibrosis