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Increased expression of ER stress genes in patients with limited cutaneous Systemic Sclerosis and Pulmonary Arterial Hypertension
Author(s) -
Lenna stefania,
Farina Alessandra G,
Martyanov Viktor,
Christmann Romy B,
Wood Tammara A,
Faber Harrison W,
Scorza Raffaella,
Whitfield Michael L,
Lafyatis Robert,
Trojanowska Maria
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1166.11
Subject(s) - unfolded protein response , immunology , xbp1 , peripheral blood mononuclear cell , gene expression , immune system , gene , medicine , biology , genetics , rna , rna splicing , in vitro
Objective Previous studies have implicated ER stress and UPR in autoimmune and inflammatory diseases.The goal of this study was to assess whether markers of ER stress/UPR are present in PBMCs from limited cutaneous systemic sclerosis (lcSSc) patients with pulmonary arterial hypertension (PAH). Methods PBMCs were purified from healthy controls (HC n=36) and lcSSc patients (n=38 with PAH and n=39 without PAH).Gene expression in HC PBMCs stimulated with ER stress inducer, thapsigargin (TG) was analyzed by DNA microarray.Expression levels of select ER stress/UPR genes and inflammation genes were analyzed by qPCR. Results ER stress/UPR genes, including BiP, transcription factors ATF4 and ATF6, and a spliced form of XBP1 were upregulated in lcSSc PBMCs, with the highest levels in patients with PAH.TG induced expression of HSPs and IFN‐regulated genes in control PBMCs.Selected HSP genes, particularly DNAJB1, and IFN‐related genes were significantly elevated in lcSSc PBMCs.There was a positive correlation between DNAJB1 and severity of PAH disease (PAP) (r = 0.59, p<0.05) and between BiP and IL‐6 levels (r = 0.64, p< 0.0001) in lcSSc PBMCs. Conclusion These studies demonstrate a possible association between ER stress/UPR gene activation and lcSSc‐PAH suggesting that ER stress/UPR contribute to the interferon signature and altered function of circulating immune cells in patients with lcSSc.