{
    "abstract": "Endoplasmic reticulum stress (ERS) and the unfolded protein response (UPR) are adaptive mechanisms for conditions of high protein demand, marked by an accumulation of misfolded proteins in the endoplasmic reticulum (ER). Rheumatic autoimmune diseases (RAD) are known to be associated with chronic inflammation and an ERS state. However, the activation of UPR signaling pathways is not completely understood in Sj\u00f6gren's disease (SD). This study evaluated the expression of ERS-related genes in glandular tissue of patients with primary SD (pSD), associated SD (aSD) with other autoimmune diseases, and non-Sj\u00f6gren sicca syndrome (NSS).\nIn a cross-sectional study, minor salivary gland biopsies were obtained from 44 patients with suspected SD and 13 healthy controls (HC). Patients were classified as pSD, aSD, or NSS based on clinical, serological, and histological assessment. Histopathological analysis and mRNA expression analysis of genes associated with ERS and UPR (PERK, XBP1, ATF-6, ATF-4, CANX, CALR, CHOP, and BIP) were performed on the samples. Differences between groups (pSD, aSD, NSS, and HC) were assessed. The influence of chloroquine (CQ) on the ER was also investigated.\nTwenty-eight SD patients showed increased expression of PERK (p\u2009=\u20090.0117) and XBP1 (p\u2009=\u20090.0346), and reduced expression of ATF-6 (p\u2009=\u20090.0003) and CHOP (p\u2009=\u20090.0003), compared to the HC group. Increased expression of BIP (p\u2009<\u20090.0001), PERK (p\u2009=\u20090.0003), CALR (p\u2009<\u20090.0001), and CANX (p\u2009=\u20090.0111) was also observed in the SD group compared to the NSS group (n\u2009=\u200916). Patients receiving CQ (n\u2009=\u200916) showed a significant increase in ATF-6 (p\u2009=\u20090.0317) compared to patients not taking the medication (n\u2009=\u200929).\nAltogether, the results suggest a greater activation of the ERS and UPR genes in patients with SD, especially in the pSD group. Antimalarial drugs, like CQ, used to treat RAD, may affect the ER function in exocrine glands.",
    "authors": [
        {
            "affiliation": "Department of Ophthalmology, Otolaryngology, Head and Neck Surgery, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil. grazivc@yahoo.com.br.\nOphthalmology, Otolaryngology, Head and Neck Surgery Department, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, Av. Bandeirantes 3900, Monte Alegre, Ribeir\u00e3o Preto, SP, 14.040-900, Brazil. grazivc@yahoo.com.br.",
            "firstname": "Graziela Vieira",
            "initials": "GV",
            "lastname": "Cavalcanti"
        },
        {
            "affiliation": "Department of Internal Medicine, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil.",
            "firstname": "Fabiola Reis",
            "initials": "FR",
            "lastname": "de Oliveira"
        },
        {
            "affiliation": "Department of Internal Medicine, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil.",
            "firstname": "Rafael Ferraz",
            "initials": "RF",
            "lastname": "Bannitz"
        },
        {
            "affiliation": "Department of Internal Medicine, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil.",
            "firstname": "Natalia Aparecida",
            "initials": "NA",
            "lastname": "de Paula"
        },
        {
            "affiliation": "Department of Stomatology, Public Health and Forensic Dentistry, Ribeir\u00e3o Preto School of Dentistry, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil.",
            "firstname": "Ana Carolina Fragoso",
            "initials": "ACF",
            "lastname": "Motta"
        },
        {
            "affiliation": "Department of Ophthalmology, Otolaryngology, Head and Neck Surgery, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil.",
            "firstname": "Eduardo Melani",
            "initials": "EM",
            "lastname": "Rocha"
        },
        {
            "affiliation": "Adeno-Associated Virus Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.",
            "firstname": "John",
            "initials": "J",
            "lastname": "Chiorini"
        },
        {
            "affiliation": "Department of Ophthalmology, Otolaryngology, Head and Neck Surgery, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil.",
            "firstname": "Hilton Marcos Alves",
            "initials": "HMA",
            "lastname": "Ricz"
        },
        {
            "affiliation": "Department of Ophthalmology, Otolaryngology, Head and Neck Surgery, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil.",
            "firstname": "Denny Marcos",
            "initials": "DM",
            "lastname": "Garcia"
        },
        {
            "affiliation": "Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, and Caswell Diabetes Institute, University of Michigan, Ann Arbor, MI, USA.",
            "firstname": "Maria Cristina",
            "initials": "MC",
            "lastname": "Foss-Freitas"
        },
        {
            "affiliation": "Department of Ophthalmology, Otolaryngology, Head and Neck Surgery, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil.",
            "firstname": "Luiz Carlos Conti",
            "initials": "LCC",
            "lastname": "de Freitas"
        }
    ],
    "conclusions": null,
    "copyrights": "\u00a9 2024. The Author(s).",
    "doi": "10.1186/s42358-024-00430-7\n10.1038/nrdp.2016.47\n10.1016/j.autrev.2018.02.009\n10.1152/ajpcell.00334.2014\n10.1146/annurev-pathol-012513-104649\n10.1002/iub.1272\n10.1007/s00018-015-2052-6\n10.1016/j.ajpath.2016.02.004\n10.1111/cei.12638\n10.1124/jpet.123.001697\n10.1093/rheumatology/kez316\n10.1097/BOR.0000000000000096\n10.1016/j.rdc.2016.03.010\n10.1038/s41584-020-0372-x\n10.1038/srep22921\n10.1152/ajpcell.1997.273.6.C2030\n10.1016/j.jaut.2016.07.006\n10.1093/rheumatology/key021\n10.1016/0030-4220(74)90417-4\n10.1038/nrneph.2017.129\n10.1155/2023/7625817\n10.1016/j.yexcr.2009.06.009\n10.1136/annrheumdis-2016-eular.1832\n10.1016/j.molimm.2007.10.023\n10.1053/sarh.2003.50019\n10.1038/s41598-020-71669-5\n10.1097/MAJ.0000000000000328\n10.1111/jcmm.13413\n10.1046/j.1365-2249.2003.02246.x\n10.1093/rheumatology/keq272\n10.4269/ajtmh.16-0138\n10.15252/emmm.202012476\n10.1080/15548627.2018.1474314\n10.1038/s41419-020-03324-w",
    "journal": "Advances in rheumatology (London, England)",
    "keywords": [
        "Cross-sectional studies",
        "Endoplasmic reticulum stress",
        "Gene expression",
        "Sj\u00f6gren syndrome",
        "Unfolded protein response"
    ],
    "methods": null,
    "publication_date": "2025-01-09",
    "pubmed_id": "39780265\n27383445\n29890347\n25540175\n25387057\n24839203\n26433683\n27085137\n25845745\n37442618\n31377809\n25050925\n27431353\n32034323\n26964637\n9435510\n30127955\n27461470\n29534223\n4589360\n28970584\n37692838\n19538957\n18022694\n12920696\n32939030\n25226532\n29160038\n12974767\n20716673\n27185766\n32715647\n29940786\n33414432",
    "results": "Twenty-eight SD patients showed increased expression of PERK (p\u2009=\u20090.0117) and XBP1 (p\u2009=\u20090.0346), and reduced expression of ATF-6 (p\u2009=\u20090.0003) and CHOP (p\u2009=\u20090.0003), compared to the HC group. Increased expression of BIP (p\u2009<\u20090.0001), PERK (p\u2009=\u20090.0003), CALR (p\u2009<\u20090.0001), and CANX (p\u2009=\u20090.0111) was also observed in the SD group compared to the NSS group (n\u2009=\u200916). Patients receiving CQ (n\u2009=\u200916) showed a significant increase in ATF-6 (p\u2009=\u20090.0317) compared to patients not taking the medication (n\u2009=\u200929).",
    "title": "Endoplasmic reticulum stress in the salivary glands of patients with primary Sj\u00f6gren's syndrome, associated Sj\u00f6gren's syndrome, and non-Sj\u00f6gren's sicca syndrome: a comparative analysis and the influence of chloroquine.",
    "xml": "<Element 'PubmedArticle' at 0x7885040c9530>"
}