PXD021715 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Ablation or Inhibition of Protein Disulfide Isomerase A3 (PDIA3) in Aberrant Club Cells Attenuates Osteopontin (SPP1) Production and Pulmonary Fibrosis |
Description | Rationale: The role of club cells in the pathology of Idiopathic Pulmonary Fibrosis IPF is not well understood. PDIA3, an endoplasmic reticulum (ER) based redox chaperone catalyzes the cysteine disulfide bonds (-S-S-) in various fibrosis-related proteins; however, mechanisms of action of PDIA3 in pulmonary fibrosis is not fully elucidated. Objectives: To examine the role of club cells and PDIA3 in the pathogenesis of pulmonary fibrosis (PF) and therapeutic potential of inhibition of PDIA3 in PF. Methods: The impact of PDIA3 and aberrant club cells in PF was studied by retrospective analysis of human transcriptome data from LGRC, and specific deletion and inhibition of PDIA3 in club cells and blocking Osteopontin (SPP1) downstream of PDIA3 in mice. Measurements and Main Results: The PDIA3 along with club cell secretory protein (SCGB1A1 or CCSP) signatures are upregulated in IPF compared to control patients, and PDIA3 increases correlate with a decrease in lung function in IPF patients. The Bleomycin (BLM) model of PF showed increases in aberrant CCSP and PDIA3 positive cells in the lung parenchyma. Ablation of Pdia3, specifically in CCSP cells, decreases CCSP cells along with PF in mice. The therapeutic administration of a PDI inhibitor LOC14 reversed the BLM-induced CCSP cells and PF in mice. The proteomic screen of the PDIA3 partners revealed SPP1 as a major interactor in PF. Blocking SPP1 attenuated the development of PF in mice. Conclusions: Collectively, this study demonstrates a new relationship of club cells, with PDIA3, SPP1, and a putative pathological function of club cells in pulmonary fibrosis. |
HostingRepository | PRIDE |
AnnounceDate | 2021-11-11 |
AnnouncementXML | Submission_2021-11-11_13:03:46.435.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD021715 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Ying Wai Lam |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-09-28 06:02:48 | ID requested | |
⏵ 1 | 2021-11-11 13:03:47 | announced | |
Publication List
Kumar A, Elko E, Bruno SR, Mark ZF, Chamberlain N, Mihavics BK, Chandrasekaran R, Walzer J, Ruban M, Gold C, Lam YW, Ghandikota S, Jegga AG, Gomez JL, Janssen-Heininger YM, Anathy V, Inhibition of PDIA3 in club cells attenuates osteopontin production and lung fibrosis. Thorax, 77(7):669-678(2022) [pubmed] |
Keyword List
submitter keyword: Pulmonary Fibrosis, IPF, CCSP, PDIA3, UPR, LOC14, Osteopontin, LC-MS/MS, spectral counting |
Contact List
Vikas Anathy |
contact affiliation | Associate Professor Dept. of Pathology and Laboratory Medicine HSRF 218, University of Vermont Larner College of Medicine Burlington, Vermont, 05405, USA |
contact email | vikas.anathy@med.uvm.edu |
lab head | |
Ying Wai Lam |
contact affiliation | Vermont Genetics Network Proteomics Facility Department of Biology University of Vermont |
contact email | ylam@uvm.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD021715
- Label: PRIDE project
- Name: Ablation or Inhibition of Protein Disulfide Isomerase A3 (PDIA3) in Aberrant Club Cells Attenuates Osteopontin (SPP1) Production and Pulmonary Fibrosis