González-Rodríguez María, Ait Edjoudi Djedjiga, Cordero Barreal Alfonso, Ruiz-Fernández Clara, Farrag Mariam, González-Rodríguez Beatriz, Lago Francisca, Capuozzo Maurizio, Gonzalez-Gay Miguel Angel, Mera Varela Antonio, Pino Jesús, Farrag Yousof, Gualillo Oreste
SERGAS (Servizo Galego de Saude), and IDIS (Instituto de Investigación Sanitaria de Santiago), NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain.
International PhD School, University of Santiago de Compostela (EDIUS), 15706 Santiago de Compostela, Spain.
Pharmaceuticals (Basel). 2022 Dec 12;15(12):1544. doi: 10.3390/ph15121544.
Progranulin (PGRN) is a glycoprotein formed by 593 amino acids encoded by the GRN gene. It has an important role in immunity and inflammatory response, as well as in tissue recovery. Its role in musculoskeletal inflammatory diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and intervertebral disc degeneration disease (IVDD), is, nowadays, an important target to investigate. The objective of this review is to systematically sum up all the recent findings concerning PGRN as a target in the development and resolution of the inflammatory diseases. PubMed was examined with the terms combinations (Progranulin) AND (Lupus Erythematosus, Systemic), (Progranulin) AND (Arthritis, Rheumatoid), and (Progranulin) AND (Intervertebral Disc Degeneration). PubMed was examined with the terms combinations (Atsttrin) AND (Lupus Erythematosus, Systemic), (Atsttrin) AND (Arthritis, Rheumatoid), and (Atsttrin) AND (Intervertebral Disc Degeneration). Moreover, research through Web of Science was performed searching the same items. The inclusion criteria were: studies whose main topic were progranulin, or atsttrin, with emphasis on the three selected diseases. On the other hand, the exclusion criteria were studies that only focused on diseases not related to RA, lupus or IVDD, in addition to the previous published literature reviews. Since few results were obtained, we did not filter by year. The records assessed for eligibility were 23, including all the studies with the information in state of art of progranulin and its capability to be a potential target or treatment for each one of the selected diseases. As these results are descriptive and not clinical trials, we did not perform risk of bias methods. Within these results, many studies have shown an anti-inflammatory activity of PGRN in RA. PGRN levels in serum and synovial fluids in RA patients were reported higher than controls. On the other hand, serum levels were directly correlated with SLE disease activity index, suggesting an important role of PGRN as a player in the progression of inflammatory diseases and a therapeutical approach for the recovery. This review has some limitations due to the small number of studies in this regard; therefore, we highlight the importance and the necessity of further investigation. No external funding was implicated in this systematical review.
颗粒蛋白前体(PGRN)是一种由GRN基因编码的含593个氨基酸的糖蛋白。它在免疫、炎症反应以及组织修复中发挥着重要作用。目前,它在类风湿关节炎(RA)、系统性红斑狼疮(SLE)和椎间盘退变疾病(IVDD)等肌肉骨骼炎症性疾病中的作用是一个重要的研究靶点。本综述的目的是系统总结关于PGRN作为炎症性疾病发生和消退靶点的所有最新研究结果。通过在PubMed上检索(颗粒蛋白前体)与(系统性红斑狼疮)、(颗粒蛋白前体)与(类风湿关节炎)以及(颗粒蛋白前体)与(椎间盘退变)的术语组合进行文献检索。同时,也通过Web of Science对相同主题进行了检索。纳入标准为:主要主题为颗粒蛋白前体或Atsttrin,且重点关注这三种选定疾病的研究。另一方面,排除标准为除先前发表的文献综述外,仅关注与RA、狼疮或IVDD无关疾病的研究。由于检索到的结果较少,我们未按年份进行筛选。评估合格的记录有23条,包括所有关于颗粒蛋白前体及其作为所选每种疾病潜在靶点或治疗方法的现有研究信息。由于这些结果是描述性的而非临床试验,我们未进行偏倚风险评估。在这些结果中,许多研究表明PGRN在RA中具有抗炎活性。RA患者血清和滑液中的PGRN水平高于对照组。另一方面,血清水平与SLE疾病活动指数直接相关,表明PGRN在炎症性疾病进展中起重要作用,且是恢复的一种治疗方法。由于这方面的研究数量较少,本综述存在一些局限性;因此,我们强调进一步研究的重要性和必要性。本系统综述未涉及外部资金。