PXD036033

PXD036033 is an original dataset announced via ProteomeXchange.

Title	System-wide vitreous proteome dissection reveals impaired sheddase activity in diabetic retinopathy
Description	Diabetic retinopathy (DR) is a major complication of diabetes mellitus causing significant vision loss. Despite the success of anti-VEGF therapy as an effective therapy, many DR patients do not respond well to the treatment, emphasizing the involvement of other molecular players. To unveil these, we performed deep vitreous proteome profiling of patients with proliferative DR and extracted aberrated protein networks. This revealed impairment in ectodomain shedding of several transmembrane proteins playing critical roles in neurodegeneration and angiogenesis, that pointed to defects in their regulating sheddases, particularly ADAM10, which emerged as the predominant sheddase. We confirmed that ADAM10 protease activity was reduced in ocular disease models and established that activation of ADAM10 can suppress endothelial cell activation and angiogenesis. Furthermore, we identified impaired ADAM10-AXL axis as a retinal angiogenic driver. Taken together, we demonstrate restoration of aberrant ectodomain shedding as an effective strategy for treating DR and propose ADAM10 as an attractive novel target.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_07:43:35.427.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Asfa Alli Shaik
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-12 13:27:36	ID requested
1	2022-10-14 14:01:21	announced
⏵ 2	2023-11-14 07:43:36	announced	2023-11-14: Updated project metadata.

Alli-Shaik A, Qiu B, Lai SL, Cheung N, Tan G, Neo SP, Tan A, Cheung CMG, Hong W, Wong TY, Wang X, Gunaratne J, System-wide vitreous proteome dissection reveals impaired sheddase activity in diabetic retinopathy. Theranostics, 12(15):6682-6704(2022) [pubmed]

submitter keyword: vitreous humor/diabetic retinopathy/ectodomain shedding/sheddase

Jayantha Gunaratne
contact affiliation	Translational Biomedical Proteomics, Institute of Molecular and Cell Biology, Singapore
contact email	jayanthag@imcb.a-star.edu.sg
lab head
Asfa Alli Shaik
contact affiliation	IMCB
contact email	asfaas@imcb.a-star.edu.sg
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/2022/10/PXD036033

PRIDE project URI

• PRIDE
  1. PXD036033
     1. Label: PRIDE project
     2. Name: System-wide vitreous proteome dissection reveals impaired sheddase activity in diabetic retinopathy