Department of Orthopaedic Surgery, New York University Medical Center, New York, NY, 10003, USA.
Department of Rheumatology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215006, PR China.
Adv Rheumatol. 2024 Sep 9;64(1):67. doi: 10.1186/s42358-024-00405-8.
Progranulin (PGRN) is a growth factor-like molecule with diverse roles in homeostatic and pathogenic processes including the control of immune and inflammatory responses. Pathogenic inflammation is a hallmark of systemic lupus erythematosus (SLE) and elevated serum levels of PGRN has been evaluated as a biomarker of disease activity in SLE. However, the role of PGRN in SLE has not been fully investigated. This study is aimed to determine the potential involvements of PGRN in SLE.
Wild type (WT) and PGRN knockout (PGRN) C57BL/6 mice received intraperitoneal injection of pristane for induction of a murine model of SLE. Sera were collected every biweekly and levels of anti-dsDNA antibody, IgG, and inflammatory factors were measured. Mice were sacrificed 5 months later and the renal lesions, as well as the proportions of T cell subtypes in the spleen were analyzed.
Following exposure to pristane, PGRN mice generated significantly lower levels of anti-dsDNA antibody and IgG relative to WT mice. PGRN mouse kidneys had less IgG and collagen deposition compared with WT mice after pristane injection.
The results indicate that PGRN participates in inflammatory response and renal damage in pristane induced SLE models, suggesting that PGRN mediates the onset of SLE.
颗粒体蛋白聚糖(PGRN)是一种具有多种功能的生长因子样分子,包括对免疫和炎症反应的控制。致病性炎症是系统性红斑狼疮(SLE)的标志,PGRN 血清水平升高已被评估为 SLE 疾病活动的生物标志物。然而,PGRN 在 SLE 中的作用尚未得到充分研究。本研究旨在确定 PGRN 在 SLE 中的潜在作用。
野生型(WT)和 PGRN 敲除(PGRN)C57BL/6 小鼠接受腹腔注射角鲨烯以诱导 SLE 小鼠模型。每两周收集一次血清,并测量抗 dsDNA 抗体、IgG 和炎症因子的水平。5 个月后处死小鼠,分析肾脏病变以及脾脏中 T 细胞亚群的比例。
暴露于角鲨烯后,PGRN 小鼠产生的抗 dsDNA 抗体和 IgG 水平明显低于 WT 小鼠。与 WT 小鼠相比,PGRN 小鼠在注射角鲨烯后肾脏的 IgG 和胶原沉积较少。
这些结果表明,PGRN 参与了角鲨烯诱导的 SLE 模型中的炎症反应和肾脏损伤,提示 PGRN 介导了 SLE 的发生。