Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Department of Vascular Biology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Pediatr Int. 2022 Jan;64(1):e15099. doi: 10.1111/ped.15099.
Dysregulation of the coagulation fibrinolysis system in resident glomerular cells is associated with the pathogenesis of lupus nephritis. However, the role of plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) in resident glomerular cells remains undetermined.
We examined the expression of PAI-1 and tPA mRNA in cultured normal human glomerular endothelial cells (GECs) treated with serum from patients with systemic lupus erythematosus (SLE) using quantitative reverse transcription polymerase chain reactions. We determined the relationship between PAI-1/tPA mRNA expression and several clinical/laboratory parameters. Serum from 16 patients (nine patients with new-onset SLE and seven patients with stable SLE) was used in the study.
Plasminogen activator inhibitor-1 and tPA mRNA expression was significantly higher in GECs treated with serum of patients with new-onset SLE than other groups. The PAI-1 and tPA mRNA levels were also significantly correlated in GECs treated with serum from patients with SLE. Interestingly, both PAI-1 and tPA mRNA levels in GECs were inversely correlated with serum C4 level and positively correlated with SLE disease activity.
These results suggest that serum from patients with SLE may activate the fibrinolysis system in glomerulus, which may be involved in the pathogenesis of lupus nephritis.
固有肾小球细胞中凝血纤溶系统的失调与狼疮肾炎的发病机制有关。然而，纤溶酶原激活物抑制剂-1（PAI-1）和组织型纤溶酶原激活物（tPA）在固有肾小球细胞中的作用仍未确定。
我们使用定量逆转录聚合酶链反应检测了用系统性红斑狼疮（SLE）患者血清处理的培养的正常人肾小球内皮细胞（GEC）中 PAI-1 和 tPA mRNA 的表达。我们确定了 PAI-1/tPA mRNA 表达与几个临床/实验室参数之间的关系。该研究使用了 16 名患者（9 名新发 SLE 患者和 7 名稳定 SLE 患者）的血清。
与其他组相比，用新发病例 SLE 患者血清处理的 GEC 中 PAI-1 和 tPA mRNA 的表达明显更高。在用 SLE 患者血清处理的 GEC 中，PAI-1 和 tPA mRNA 水平也呈显著相关。有趣的是，GEC 中的 PAI-1 和 tPA mRNA 水平与血清 C4 水平呈负相关，与 SLE 疾病活动呈正相关。
这些结果表明，SLE 患者的血清可能激活肾小球中的纤溶系统，这可能与狼疮肾炎的发病机制有关。
