title: Expression of glucocorticoid receptor isoforms and associations with serine/arginine-rich protein 30c and 40 in patients with systemic lupus erythematosus.
abstract: OBJECTIVE
  To investigate the expression of glucocorticoid receptor (GR) isoforms in patients with systemic lupus erythematosus (SLE), confirm the main GR isoforms involving in glucocorticoids (GC) resistance, and explore the associations of GR isoforms with serine/arginine-rich protein (SRp) 30c and SRp40.
  
  
  METHODS
  Seventy patients with SLE and thirty-eight age- and sex-matched controls were recruited. All patients received prednisone (0.5-1 mg/kg/d) as their routine therapy. According to the therapeutic effect, patients were divided into glucocorticoid-resistant (GCR) and glucocorticoid-sensitive (GCS) groups. Transcript levels of GRα, GRβ, GRγ, GR-P, SRp30c and SRp40 in peripheral blood mononuclear cells (PBMCs) were determined by real-time PCR. GRα and GRβ proteins were detected by western blotting. Trial registration number is ChiCTR-RCH-12002808.
  
  
  RESULTS
  Four GR transcripts in SLE patients showed the following trend: GRα (51.85%) > GR-P (23.78%) > GRγ (13.08%) >GRβ (0.03%). GR-P transcript and ratio of GRα/GR-P in SLE patients were significantly higher than that in controls (p<0.05). GRα transcript and protein as well as SRp40 transcript in GCS group were significantly higher than that in the GCR group before GC treatment (p<0.05). In the GCS group, GRα transcript and SRp40 transcript were significantly higher after GC treatment than that before GC treatment (p<0.05). In the GCR group, GR-P transcript was significantly higher after GC treatment than that before GC treatment (p<0.05). Positive correlation between SRp40 and GRα transcript was found (p<0.05). Additionally, SLE Disease Activity Index scores were significantly negatively correlated with GRα transcript and protein expression (p<0.05).
  
  
  CONCLUSIONS
  Our data demonstrated that the decreased expression of GRα might be the evidence of high disease activity and help to predict GC resistance. GR-P isoform might be implicated in the development of resistance. Additionally, the preliminary finding suggested that SRp40 might be associated with GRα transcripts in SLE patients.
authors: Department of Rheumatology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
authors: Yan-Chun
authors: YC
authors: Guan
authors: Department of Rheumatology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
authors: Lei
authors: L
authors: Jiang
authors: Department of Rheumatology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
authors: Liang-Liang
authors: LL
authors: Ma
authors: Department of Rheumatology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
authors: Xiang-Nan
authors: XN
authors: Sun
authors: Department of Rheumatology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
authors: Dan-Dan
authors: DD
authors: Yu
authors: Regenerative Medicine Center, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
authors: Jing
authors: J
authors: Liu
authors: Department of Haematology, Dalian Friendship Hospital, Dalian, China.
authors: Dong-Xia
authors: DX
authors: Qu
authors: Department of Rheumatology, The First Affiliated Hospital of Dalian Medical University; and College of Lab Medicine, Dalian Medical University, Dalian, China.
authors: Mei-Yun
authors: MY
authors: Fang
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004351:Drug Resistance; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000097:blood* / Q000235:genetics; D011237:Predictive Value of Tests; D011241:Prednisone / Q000627:therapeutic use; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000097:blood; D016601:RNA-Binding Proteins / Q000097:blood* / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000819:agonists / Q000097:blood* / Q000235:genetics; D012307:Risk Factors; D000068103:Serine-Arginine Splicing Factors; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; C497471:GRgamma protein, human; D005938:Glucocorticoids; C497713:NR3C1 protein, human; D009687:Nuclear Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; C121943:glucocorticoid receptor beta; D000068103:Serine-Arginine Splicing Factors; D011241:Prednisone