PXD035504

PXD035504 is an original dataset announced via ProteomeXchange.

Title	A discovery-based proteomics approach identifies protein disulfide isomerase (PDIA1) as a biomarker of β cell stress in type 1 diabetes
Description	Background: Activation of stress pathways intrinsic to the β cell are thought to both accelerate β cell death and increase β cell immunogenicity in type 1 diabetes (T1D). However, information on the timing and scope of these responses is lacking. Methods: To identify temporal and disease-related changes in islet β cell protein expression, SWATH-MS/MS proteomics analysis was performed on islets collected longitudinally from NOD mice and NOD-SCID mice rendered diabetic through T cell adoptive transfer. Findings: In islets collected from female NOD mice at 10, 12, and 14 weeks of age, we found a time-restricted upregulation of proteins involved in the maintenance of β cell function and stress mitigation, followed by loss of expression of protective proteins that heralded diabetes onset. Pathway analysis identified EIF2 signaling and the unfolded protein response, mTOR signaling, mitochondrial function, and oxidative phosphorylation as commonly modulated pathways in both diabetic NOD mice and NOD-SCID mice rendered acutely diabetic by adoptive transfer, highlighting this core set of pathways in T1D pathogenesis. In immunofluorescence validation studies, β cell expression of protein disulfide isomerase A1 (PDIA1) and 14-3-3b were found to be increased during disease progression in NOD islets, while PDIA1 plasma levels were increased in pre-diabetic NOD mice and in the serum of children with recent-onset T1D compared to age and sex-matched non-diabetic controls. Interpretation: We identified a common and core set of modulated pathways across distinct mouse models of T1D and identified PDIA1 as a potential human biomarker of β cell stress in T1D.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:43:34.420.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Niveda Sundararaman
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	TripleTOF 6600

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-21 08:20:14	ID requested
1	2023-03-11 10:10:32	announced
⏵ 2	2023-11-14 08:43:41	announced	2023-11-14: Updated project metadata.

Syed F, Singhal D, Raedschelders K, Krishnan P, Bone RN, McLaughlin MR, Van Eyk JE, Mirmira RG, Yang ML, Mamula MJ, Wu H, Liu X, Evans-Molina C, cell stress in type 1 diabetes. EBioMedicine, 87():104379(2023) [pubmed]

submitter keyword: proteomics,β cell stress, protein disulfide isomerase A1, biomarkers, type 1 diabetes

Jennifer Van Eyk
contact affiliation	Heart Institute, Cedars-Sinai Medical Center
contact email	Jennifer.VanEyk@cshs.org
lab head
Niveda Sundararaman
contact affiliation	Cedars Sinai Medical Center
contact email	Niveda.Sundararaman@cshs.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035504
     1. Label: PRIDE project
     2. Name: A discovery-based proteomics approach identifies protein disulfide isomerase (PDIA1) as a biomarker of β cell stress in type 1 diabetes