Department of Molecular Biology, Faculty of Medicine, Semmelweis University, Budapest, 1085, Hungary.
Department of Clinical Pathology and Oncology, University of Veterinary Medicine, Budapest, 1078, Hungary.
Sci Rep. 2021 Dec 30;11(1):24505. doi: 10.1038/s41598-021-03451-0.
Glucocorticoids play a central role in the inflammatory response and alleviate the symptoms in critically ill patients. The glucocorticoid action relies on the glucocorticoid receptor (GR) which translocates into the nucleus upon ligand-binding and regulates transcription of a battery of genes. Although the GR is encoded by a single gene, dozens of its splice variants have been described in diverse species. The GRα isoform encodes the full, functionally active protein that is composed of a transactivation, a DNA-binding, and a C-terminal ligand-binding domain. The second most highly expressed receptor variant, the GR-P, is formed by an intron retention that introduces an early stop codon and results in a probably dysfunctional protein with truncated ligand-binding domain. We described the canine ortholog of GR-P and showed that this splice variant is highly abundant in the peripheral blood of dogs. The level of cGRα and cGR-P transcripts are elevated in patients of SIRS and the survival rate is increased with elevated cGRα and cGR-P expression. The ratio of cGRα and cGR-P mRNA did not differ between the survivor and non-survivor patients; thus, the total GR expression is more pertinent than the relative expression of GR isoforms in assessment of the disease outcome.
糖皮质激素在炎症反应中起着核心作用，并能缓解重症患者的症状。糖皮质激素的作用依赖于糖皮质激素受体（GR），它在配体结合后易位到细胞核内，并调节一系列基因的转录。尽管 GR 是由单个基因编码的，但在不同的物种中已经描述了数十种其剪接变体。GRα 异构体编码完整的、功能活跃的蛋白质，由转录激活、DNA 结合和 C 端配体结合域组成。表达量第二高的受体变体 GR-P 是通过内含子保留形成的，这导致提前出现终止密码子，并产生一个可能功能失调的蛋白，其配体结合域被截断。我们描述了犬科 GR-P 的同源物，并表明这种剪接变体在犬的外周血中高度丰富。SIRS 患者的 cGRα 和 cGR-P 转录本水平升高，cGRα 和 cGR-P 表达升高的患者存活率增加。存活者和非存活者患者之间的 cGRα 和 cGR-P mRNA 比值没有差异；因此，在评估疾病结果时，总 GR 表达比 GR 异构体的相对表达更相关。
