PRL-R ISOFORMS LONG / SHORT RATIO IS INCREASED IN SYSTEMIC LUPUS ERYTHEMATOSUS BLOOD MONONUCLEAR CELLS

María Tamara Moreno-Sosa, Daiana Sthefania Garcia, Rocío Heredia, Victor BITTAR-RIVERO-PEDROSA, J. Mackern-Oberti
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Abstract

Prolactin (PRL) displays several functions in the whole body by binding its receptor (PRL-R). Two main PRL-R isoforms are reported that differ in their capacity to trigger signaling pathways, PRL-R long isoform is the activation receptor, and the short isoform is the inhibitory oner. Although many autoimmune diseases display hyperprolactinemia, the role of each PRL-R isoform expression in autoimmunity remains unknown. This work aimed to correlate PRL-R isoforms expression in human peripheral blood mononuclear cells (PBMCs) of female Systemic Lupus Erythematosus patients and healthy controls. To this end, PBMCs from lupus patients (n=9) and healthy controls (n=5) were enriched by the ficoll-hypaque method. Then, RNA extraction, cDNA synthesis, and real-time PCR were performed to determine mRNA expression. We found that PRL-R long and short isoforms expression from lupus patients display similar expression to healthy controls. However, the PRL-RL/PRL-RS ratio is higher than healthy controls (P-value two-tailed <0,05). Additionally, PRL-RL isoform expression correlates with the short isoform in lupus patients (Spearman r 0,8945; 95% confidence interval 0,6834 to 0,9676; P-value two-tailed <0,0001). However, the expression of neither long and short isoforms correlates with active disease nor disease duration. Similarly, lupus patients display similar PRL-R isoforms expression than healthy controls. Although much work must be done, our data indicate that similar mechanisms may regulate the expression of both PRL-R isoforms in immune cells, and “their expression goes hand by hand”. , ,
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系统性红斑狼疮血单个核细胞中Prl-r亚型长/短比值增高
催乳素(PRL)通过与其受体(PRL- r)结合,在全身发挥多种功能。据报道,两种主要的PRL-R异构体在触发信号通路的能力上存在差异,PRL-R长异构体是激活受体,短异构体是抑制受体。虽然许多自身免疫性疾病表现为高泌乳素血症,但每种PRL-R异构体表达在自身免疫中的作用尚不清楚。本研究旨在探讨女性系统性红斑狼疮患者和健康对照者外周血单个核细胞(PBMCs)中PRL-R亚型表达的相关性。为此,采用ficoll-hypaque方法对狼疮患者(n=9)和健康对照(n=5)的PBMCs进行富集。然后进行RNA提取、cDNA合成和实时荧光定量PCR检测mRNA表达。我们发现狼疮患者的PRL-R长、短异构体表达与健康对照相似。但PRL-RL/PRL-RS比值高于健康对照组(双尾p值< 0.05)。此外,狼疮患者PRL-RL亚型表达与短亚型相关(Spearman r 0,8945;95%置信区间为0.6834 ~ 0.9676;p值双尾<0,0001)。然而,无论是长亚型还是短亚型的表达都与活动性疾病或病程无关。同样,狼疮患者的PRL-R亚型表达与健康对照组相似。虽然还有很多工作要做,但我们的数据表明,类似的机制可能调节免疫细胞中两种PRL-R亚型的表达,并且“它们的表达是密切相关的”。, ,
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