Guan Yan-Chun, Jiang Lei, Ma Liang-Liang, Sun Xiang-Nan, Yu Dan-Dan, Liu Jing, Qu Dong-Xia, Fang Mei-Yun
Department of Rheumatology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
Regenerative Medicine Center, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
Clin Exp Rheumatol. 2015 Mar-Apr;33(2):225-33. Epub 2015 Feb 9.
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.
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.
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).
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.
研究糖皮质激素受体（GR）亚型在系统性红斑狼疮（SLE）患者中的表达，确定参与糖皮质激素（GC）抵抗的主要GR亚型，并探讨GR亚型与富含丝氨酸/精氨酸蛋白（SRp）30c和SRp40的相关性。
招募70例SLE患者和38例年龄及性别匹配的对照。所有患者接受泼尼松（0.5 - 1mg/kg/d）作为常规治疗。根据治疗效果，将患者分为糖皮质激素抵抗（GCR）组和糖皮质激素敏感（GCS）组。采用实时PCR检测外周血单个核细胞（PBMCs）中GRα、GRβ、GRγ、GR - P、SRp30c和SRp40的转录水平。通过蛋白质印迹法检测GRα和GRβ蛋白。试验注册号为ChiCTR - RCH - 12002808。
SLE患者的四种GR转录本呈现以下趋势：GRα（51.85%）> GR - P（23.78%）> GRγ（13.08%）> GRβ（0.03%）。SLE患者的GR - P转录本及GRα/GR - P比值显著高于对照组（p<0.05）。GC治疗前，GCS组的GRα转录本、蛋白以及SRp40转录本显著高于GCR组（p<0.05）。在GCS组中，GC治疗后GRα转录本和SRp40转录本显著高于GC治疗前（p<0.05）。在GCR组中，GC治疗后GR - P转录本显著高于GC治疗前（p<0.05）。发现SRp40与GRα转录本呈正相关（p<0.05）。此外，SLE疾病活动指数评分与GRα转录本和蛋白表达呈显著负相关（p<0.05）。
我们的数据表明，GRα表达降低可能是疾病活动度高的证据，并有助于预测GC抵抗。GR - P亚型可能与抵抗的发生有关。此外，初步研究结果表明，SRp40可能与SLE患者的GRα转录本相关。
