Ask about this productRelated genes to: PDIA4 antibody
- Gene:
- PDIA4 NIH gene
- Name:
- protein disulfide isomerase family A member 4
- Previous symbol:
- -
- Synonyms:
- ERP70, ERP72
- Chromosome:
- 7q36.1
- Locus Type:
- gene with protein product
- Date approved:
- 2005-03-02
- Date modifiied:
- 2016-10-05
Related products to: PDIA4 antibody
Related articles to: PDIA4 antibody
- A strong crosstalk exists between endoplasmic reticulum (ER) stress and synovitis. Beyond their canonical role in protein folding, ER stress chaperones may promote inflammation, cell survival, and fibroblast activation under pathological conditions. This study aimed at localizing and quantifying 11 ER stress proteins (BiP, HYOU1, MANF, PDIA4, GANAB, HSP90B1, TXNDC5, DNAJB11, LMAN1, ERP29, CALR) in human inflamed synovial membranes and at investigating their expression in fibroblast-like synoviocytes (FLS) under ER stress, pro-inflammatory, or pro-fibrotic stimuli. By immunohistochemistry, on a first cohort of formalin-fixed paraffin-embedded (FFPE) biopsies obtained from patients with osteoarthritis (OA), chronic pyrophosphate arthropathy (CPPA), and rheumatoid arthritis (RA), these ER chaperones were primarily localized to the lining in low-grade inflammation (Tak <4) and expanded to the sublining under high inflammatory conditions (Tak ≥4), with a widespread distribution in RA. Imaging mass cytometry, applied to a second cohort of FFPE tissue samples collected from patients diagnosed with OA and RA, revealed the co-expression of ER stress proteins with CD55⁺ FLS in the lining and their progressive infiltration into the sublining along with CD34⁺CD31 FLS during inflammation. These observations were confirmed by immunofluorescence on a larger cohort of OA patients. As inflammation progresses, there is a loss of co-expression with CD55 in the lining, accompanied by a gradual shift towards co-expression with CD34 in the sublining. In vitro, ER stress proteins, particularly BiP, HYOU1, MANF, PDIA4, HSP90B1, LMAN1, CALR, and DNAJB11 are overexpressed in human OA FLS following ER stress, pro-inflammatory or pro-fibrotic stimulation, with BiP, PDIA4, HSP90B1, ERP29, and CALR also being secreted. PDIA4 emerged as a central player: its depletion significantly impaired FLS proliferation and migration, highlighting a direct role in driving synovitis. This study provides the first spatial and functional characterization of ER chaperones in human arthritic synovium, linking ER stress to fibroblast plasticity, inflammation, and fibrosis. - Source: PubMed
Publication date: 2026/08/12
Gendebien ZoéPoulet ChristopheDeroyer CélinePaulissen GenevièveSalpetier PaulineHego AlexandreLefèvre GaëtanCobraiville GaëlNeuville SophiePlener ZeldaDaniel ChristopheThirion ThierrySokolova TatianaDurez PatrickHemon PatriceDelarue YunaMarec NadègeBianchi ElettraDelvenne PhilippeRibbens Cliode Seny Dominique - Oxidative stress and inflammation, and the accumulation of unfolded proteins are primary causes in the pathophysiology of peripheral artery disease (PAD), which develops in the presence of type 2 diabetes mellitus (T2DM), characterized by hyperglycemia and insulin resistance. It has been reported that the interaction between endoplasmic reticulum (ER) stress protein, protein disulfide isomerase (PDIA4), and receptor for advanced glycation end products (RAGE) make significant contributions to these processes. Our study aimed to investigate variations in the -2 rs35652124 and -2 rs6721961 polymorphic regions in PAD and examine the relationship between these variations and RAGE and PDIA4 protein levels. - Source: PubMed
Publication date: 2026/07/07
Kara Hatice ZühreYanar FatihPunar ŞeymaAbacı NeslihanEkmekçi Sema SırmaBaşar YılmazSalmayenli NihalÖzkök Elif - Breast cancer remains a leading cause of cancer-related mortality in women, and current prognostic models are suboptimal. The transcriptomic role of programmed cell death (PCD) in breast cancer progression is not fully understood. Here, we integrated single-cell RNA sequencing data from breast tumors with nine bulk transcriptomic cohorts to systematically analyze 19 PCD modalities. Using a machine learning framework incorporating 14 algorithms, we constructed a prognostic signature, with a ridge regression-based PCD riskscore showing optimal performance and being further integrated into a clinical nomogram. Functional roles of key genes were validated through and experiments. We identified a prognostic signature comprising 26 core PCD genes, which effectively stratified patients into distinct risk groups and robustly predicted overall survival. Single-cell analyses revealed that a high PCD risk core was associated with an immunosuppressive tumor microenvironment and reduced immune checkpoint expression, whereas low-risk patients showed greater sensitivity to targeted therapies. Among the signature genes, was consistently overexpressed in 50 paired breast cancer tissues, and its knockdown markedly inhibited tumor growth and malignant phenotypes. This study establishes a novel PCD-based prognostic signature for breast cancer and identifies as a functionally important oncogene. - Source: PubMed
Publication date: 2026/07/25
Jiang JixuanWang YiwenHuang YujuYan WeiwenLi ShuweiWang Ruoxi - Cervical cancer continues to pose a considerable challenge to global health, necessitating innovative approaches for improved diagnostics and personalized treatment strategies. Prior investigations have suggested that plasma proteins may play a role in the pathogenesis of cervical cancer; however, these studies do not confirm a causal relationship. To address this gap, conducted a large-scale Mendelian randomization (MR) study of the plasma proteome. - Source: PubMed
Publication date: 2026/07/01
Zhao Yan-HongRuan Qing-FenNing Jing-HuaZhang XinQu RunZou JingLiang YiZhang Cheng-GuiZhang Yu-Zhe - We applied the TempO-LINC® platform to generate single-cell transcriptomic (SCTr) profiles of ∼40,000 HepaRG cells exposed to etoposide, brefeldin A, cycloheximide, rotenone, tBHQ, troglitazone, and tunicamycin at three concentrations for 24 hours. SCTr enabled a detailed analysis of adaptive stress response pathways (SRPs), including the unfolded protein response (UPR), oxidative stress response (OSR), heat shock response (HSR), and DNA damage response (DDR). Troglitazone upregulated lipid metabolism genes () along with HSR and UPR activation, with co-expression of , and in subsets of cells. Brefeldin A and tunicamycin strongly induced UPR markers () in subsets of cells, with some also expressing apoptotic () and autophagic () genes, indicating diverse stress responses. Rotenone activated , and in a fraction of cells, accompanied by and mild UPR induction, reflecting heterogeneous mitochondrial stress responses. We scored individual cells using literature-derived SRP gene signatures to characterize overall stress phenotypes and clustered them using a generalized Jaccard metric. The clustering revealed five phenotypic groups spanning cell states associated with homeostasis, adaptive responses, terminal outcomes, autophagy, and apoptosis. By systematically analyzing the distributions of cells in different states across treatments, we visualized dynamic shifts in cellular subpopulations responding to chemicals, revealing early stress responses and potential transitions to cell death. Our findings suggest the utility of SCTr in decoding stress states that could provide possible insights into transitions between cellular adaptive and terminal transitions involved in toxicity. - Source: PubMed
Publication date: 2025/08/26
Shah ImranGallegos DavidRobinette BrianChambers Bryant AEastburn Dennis JBell Douglas ACampbell Michelle RMartos Suzanne NCamiolo SalvatoreWhite Kevin SMartin NicoleMontis GioeleMcComb JoelSeligmann BruceChorley Brian N