Liang Yan, Song Meng Meng, Liu Shi Yan, Ma Liang Liang
a Department of Hematology/Oncology , Tai'an Hospital of Traditional Chinese Medicine (TCM) , Tai'an 271000 , Shandong Province , China.
b Department of Hematology , First Affiliated Hospital of Dalian Medical University , Dalian 116011 , Liaoning Province , China.
Hematology. 2016 Aug;21(7):440-6. doi: 10.1080/10245332.2015.1102371. Epub 2016 Mar 21.
Glucocorticoids (GCs) play an important role in the treatment of several hematological malignancies, such as immune thrombocytopenia (ITP). The glucocorticoid receptor (GR) mediates the effects of GCs. Five isoforms of GR mRNA were described: GRα, GRβ, GRγ, GRP, and GRA. GR levels are regulated by alternative splicing of GR mRNA. Several studies demonstrated that a lower GR expression was associated with poor GC response.
This study investigated the expression of GR isoforms and the relationship between GC resistance in ITP.
This study determined GRα/β/γ/P mRNA and GRα/β protein expression levels using SYBR Green Real-time PCR and Western blot, respectively, in 49 newly diagnosed ITP patients and 31 controls.
The expression of GR isoform mRNA in ITP and controls showed the following trend: GRα > GRP > GRγ > GRβ. The expression of GRα, β mRNA and the total frequency of the four GR isoforms in ITP was significantly higher than in controls (P < 0.05). The expression of GRα mRNA and protein in the GC-resistant group was significantly lower than that in the GC-sensitive group and controls (P < 0.05). GRβ could not be detected at the protein level in our experimental conditions.
GRα and GRP were the main GR isoforms responsible for the effects of GC, and GRα and GRP exhibited synergistic effects. The down-regulation of GRα levels may play an important role in GC resistance in ITP. The effects of GCs in ITP were not associated with changes in GRβ and GRγ.
糖皮质激素（GCs）在多种血液系统恶性肿瘤的治疗中发挥重要作用，如免疫性血小板减少症（ITP）。糖皮质激素受体（GR）介导GCs的作用。已描述了GR mRNA的五种异构体：GRα、GRβ、GRγ、GRP和GRA。GR水平受GR mRNA可变剪接的调节。多项研究表明，较低的GR表达与GC反应不佳相关。
本研究调查ITP中GR异构体的表达及与GC抵抗的关系。
本研究分别采用SYBR Green实时PCR和蛋白质印迹法，测定49例新诊断ITP患者和31例对照者的GRα/β/γ/P mRNA及GRα/β蛋白表达水平。
ITP患者和对照者中GR异构体mRNA的表达呈现以下趋势：GRα＞GRP＞GRγ＞GRβ。ITP患者中GRα、β mRNA的表达及四种GR异构体的总频率显著高于对照者（P＜0.05）。GC抵抗组中GRα mRNA和蛋白的表达显著低于GC敏感组和对照者（P＜0.05）。在我们的实验条件下，未在蛋白水平检测到GRβ。
GRα和GRP是介导GC作用的主要GR异构体，且GRα和GRP表现出协同作用。GRα水平下调可能在ITP的GC抵抗中起重要作用。GCs在ITP中的作用与GRβ和GRγ的变化无关。
