PXD018728

PXD018728 is an original dataset announced via ProteomeXchange.

Title	Connectivity mapping of glomerular proteins identifies dimethylaminoparthenolide as a new inhibitor of diabetic kidney disease
Description	While blocking the renin angiotensin aldosterone system (RAAS) has been the main therapeutic strategy to control diabetic kidney disease (DKD) for many years, 25-30% of diabetic patients still develop the disease. In the present work we adopted a system biology strategy to analyze glomerular protein signatures to identify drugs with potential therapeutic properties in DKD acting through a RAAS-independent mechanism. Glomeruli were isolated from wild type and type 1 diabetic mice (Ins2Akita) treated or not with the angiotensin-converting enzyme inhibitor (ACEi) ramipril. Ramipril efficiently reduced the urinary albumin/creatine ratio (ACR) of Ins2Akita mice without modifying DKD-associated renal-injuries. Large scale quantitative proteomics was used to identify the DKD-associated glomerular proteins (DKD-GPs) that were ramipril-insensitive (RI-DKD-GPs). We then applied an in silico drug repurposing approach using a pattern-matching algorithm (Connectivity Mapping) to compare the RI-DKD-GPs’s signature with a collection of thousands of transcriptional signatures of bioactive compounds. The sesquiterpene lactone parthelonide was identified as one of the top compounds predicted to reverse the RI-DKD-GPs’s signature. Treatment of diabetic Ins2Akita mice with dimethylaminoparthenolide (DMAPT), a water soluble analogue of parthenolide, significantly reduced urinary ACR. However, in contrast to ramipril, DMAPT also significantly reduced glomerulosclerosis and tubulointerstitial fibrosis. Using a system biology approach we identified DMAPT, as a compound with a potential add-on value to standard-of-care ACEi-treatment in DKD.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:12:25.798.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Emmanuelle Mouton Barbosa
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-22 05:17:37	ID requested
1	2020-09-17 04:10:04	announced
⏵ 2	2024-10-22 05:12:27	announced	2024-10-22: Updated project metadata.

10.1038/s41598-020-71950-7;

Klein J, Caubet C, Camus M, Makridakis M, Denis C, Gilet M, Feuillet G, Rascalou S, Neau E, Garrigues L, Thillaye du Boullay O, Mischak H, Monsarrat B, Burlet-Schiltz O, Vlahou A, Saulnier-Blache JS, Bascands JL, Schanstra JP, Connectivity mapping of glomerular proteins identifies dimethylaminoparthenolide as a new inhibitor of diabetic kidney disease. Sci Rep, 10(1):14898(2020) [pubmed]

submitter keyword: quantitative proteomics, nephropathy,Diabetic kidney disease

Joost P. Schanstra
contact affiliation	Institut National de la Santé et de la Recherche Médicale (INSERM), U1048, Institut of Cardiovascular and Metabolic Disease, Toulouse, France. Université Toulouse III Paul-Sabatier, Toulouse, France.
contact email	joost-peter.schanstra@inserm.fr
lab head
Emmanuelle Mouton Barbosa
contact affiliation	IPBS CNRS
contact email	emmanuelle.mouton@ipbs.fr
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/2020/09/PXD018728

PRIDE project URI

• PRIDE
  1. PXD018728
     1. Label: PRIDE project
     2. Name: Connectivity mapping of glomerular proteins identifies dimethylaminoparthenolide as a new inhibitor of diabetic kidney disease