Progranulin mediates the onset of pristane induced systemic lupus erythematosus

IF 2 4区 医学 Q3 RHEUMATOLOGY
Michun He, Aubryanna Hettinghouse, Yufei Bi, Yuehong Chen, Chuanju Liu
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Abstract

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.
Progranulin 介导了普利斯坦诱导的系统性红斑狼疮的发病
Progranulin(PGRN)是一种生长因子样分子,在体内平衡和致病过程中具有多种作用,包括控制免疫和炎症反应。致病性炎症是系统性红斑狼疮(SLE)的特征之一,血清中 PGRN 水平的升高已被评估为系统性红斑狼疮疾病活动的生物标志物。然而,PGRN 在系统性红斑狼疮中的作用尚未得到充分研究。本研究旨在确定 PGRN 在系统性红斑狼疮中的潜在作用。野生型(WT)和PGRN基因敲除(PGRN-/-)C57BL/6小鼠腹腔注射普利斯坦,诱导建立小鼠系统性红斑狼疮模型。每两周收集一次血清,测定抗dsDNA抗体、IgG和炎症因子的水平。5 个月后小鼠被处死,并对肾脏病变和脾脏中 T 细胞亚型的比例进行分析。与WT小鼠相比,暴露于普利斯坦后,PGRN-/-小鼠产生的抗dsDNA抗体和IgG水平明显较低。与WT小鼠相比,PGRN-/-小鼠肾脏在注射普利斯坦后的IgG和胶原沉积较少。结果表明,PGRN 参与了普利斯坦诱导的系统性红斑狼疮模型的炎症反应和肾损伤,这表明 PGRN 介导了系统性红斑狼疮的发病。
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来源期刊
Advances in Rheumatology
Advances in Rheumatology Medicine-Rheumatology
CiteScore
4.00
自引率
4.30%
发文量
41
审稿时长
53 weeks
期刊介绍: Formerly named Revista Brasileira de Reumatologia, the journal is celebrating its 60th year of publication. Advances in Rheumatology is an international, open access journal publishing pre-clinical, translational and clinical studies on all aspects of paediatric and adult rheumatic diseases, including degenerative, inflammatory and autoimmune conditions. The journal is the official publication of the Brazilian Society of Rheumatology and welcomes original research (including systematic reviews and meta-analyses), literature reviews, guidelines and letters arising from published material.
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