Chen Chunyan, Zhang Jingwei, Yu Tao, Feng Haiya, Liao Jian, Jia Yifei
Department of Nephrology, Jiaxing Hospital of Traditional Chinese Medicine, Jiaxing, China.
Department of Urology, Guangzhou First People's Hospital, Guangzhou, China.
Kidney Dis (Basel). 2024 Apr 3;10(3):237-248. doi: 10.1159/000538443. eCollection 2024 Jun.
The increasing prevalence of kidney diseases has become a significant public health issue, with a global prevalence exceeding 10%. In order to accurately identify biochemical changes and treatment outcomes associated with kidney diseases, novel methods targeting specific genes have been discovered. Among these genes, leucine-rich α-2 glycoprotein 1 (LRG1) has been identified to function as a multifunctional pathogenic signaling molecule in multiple diseases, including kidney diseases. This study aims to provide a comprehensive overview of the current evidence regarding the roles of LRG1 in different types of kidney diseases.
Based on a comprehensive review, it was found that LRG1 was upregulated in the urine, serum, or renal tissues of patients or experimental animal models with multiple kidney diseases, such as diabetic nephropathy, kidney injury, IgA nephropathy, chronic kidney diseases, clear cell renal cell carcinoma, end-stage renal disease, canine leishmaniosis-induced kidney disease, kidney fibrosis, and aristolochic acid nephropathy. Mechanistically, the role of LRG1 in kidney diseases is believed to be detrimental, potentially through its regulation of various genes and signaling cascades, i.e., fibronectin 1, GPR56, vascular endothelial growth factor (VEGF), VEGFR-2, death receptor 5, GDF15, HIF-1α, SPP1, activin receptor-like kinase 1-Smad1/5/8, NLRP3-IL-1b, and transforming growth factor β pathway.
Further research is needed to fully comprehend the molecular mechanisms by which LRG1 contributes to the pathogenesis and pathophysiology of kidney diseases. It is anticipated that targeted treatments focusing on LRG1 will be utilized in clinical trials and implemented in clinical practice in the future.
肾脏疾病的患病率不断上升已成为一个重大的公共卫生问题,全球患病率超过10%。为了准确识别与肾脏疾病相关的生化变化和治疗结果,已发现了针对特定基因的新方法。在这些基因中,富含亮氨酸的α-2糖蛋白1(LRG1)已被确定在包括肾脏疾病在内的多种疾病中作为多功能致病信号分子发挥作用。本研究旨在全面概述目前关于LRG1在不同类型肾脏疾病中作用的证据。
基于全面的综述发现,在患有多种肾脏疾病的患者或实验动物模型的尿液、血清或肾组织中,LRG1表达上调,这些疾病包括糖尿病肾病、肾损伤、IgA肾病、慢性肾脏疾病、透明细胞肾细胞癌、终末期肾病、犬利什曼病诱导的肾病、肾纤维化和马兜铃酸肾病。从机制上讲,LRG1在肾脏疾病中的作用被认为是有害的,可能是通过其对各种基因和信号级联的调控,即纤连蛋白1、GPR56、血管内皮生长因子(VEGF)、VEGFR-2、死亡受体5、GDF15、HIF-1α、SPP1、激活素受体样激酶1-Smad1/5/8、NLRP3-IL-1b和转化生长因子β途径。
需要进一步研究以充分理解LRG1促成肾脏疾病发病机制和病理生理学的分子机制。预计未来将在临床试验中采用针对LRG1的靶向治疗并在临床实践中实施。