⮝ Full datasets listing

PXD018728

PXD018728 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleConnectivity mapping of glomerular proteins identifies dimethylaminoparthenolide as a new inhibitor of diabetic kidney disease
DescriptionWhile 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.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:12:25.798.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterEmmanuelle Mouton Barbosa
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListNo PTMs are included in the dataset
InstrumentLTQ Orbitrap
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-04-22 05:17:37ID requested
12020-09-17 04:10:04announced
22024-10-22 05:12:27announced2024-10-22: Updated project metadata.
Publication List
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]
Keyword List
submitter keyword: quantitative proteomics, nephropathy,Diabetic kidney disease
Contact List
Joost P. Schanstra
contact affiliationInstitut 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 emailjoost-peter.schanstra@inserm.fr
lab head
Emmanuelle Mouton Barbosa
contact affiliationIPBS CNRS
contact emailemmanuelle.mouton@ipbs.fr
dataset submitter
Full Dataset Link List
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
Repository Record List
[ + ]