Krizanac Marinela, Mass Sanchez Paola Berenice, Weiskirchen Ralf, Schröder Sarah K
Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, Aachen, Germany.
Front Endocrinol (Lausanne). 2024 Apr 5;15:1365602. doi: 10.3389/fendo.2024.1365602. eCollection 2024.
The 25 kDa-sized protein Lipocalin 2 (LCN2) was originally isolated from human neutrophil granulocytes more than 30 years ago. LCN2 is an emerging player in innate immune defense, as it reduces bacterial growth due to its ability to sequester iron-containing bacterial siderophores. On the other hand, LCN2 also serves as a transporter for various hydrophobic substances due to its β-barrel shaped structure. Over the years, LCN2 has been detected in many other cell types including epithelial cells, astrocytes, and hepatocytes. Studies have clearly shown that aberrant expression of LCN2 is associated with a variety of disorders and malignancies, including several diseases of the reproductive system. Furthermore, LCN2 was proposed as a non-invasive prognostic and/or diagnostic biomarker in this context. Although several studies have shed light on the role of LCN2 in various disorders of the female and male reproductive systems, including tumorigenesis, a comprehensive understanding of the physiological function of LCN2 in the reproductive tract is still lacking. However, there is evidence that LCN2 is directly related to fertility, as global depletion of in mice has a negative effect on their pregnancy rate. Since LCN2 expression can be regulated by steroid hormones, it is not surprising that its expression fluctuates greatly during remodeling processes in the female reproductive tract, especially in the uterus. Well-founded details about the expression and regulation of LCN2 in a healthy reproductive state and also about possible changes during reproductive aging could contribute to a better understanding of LCN2 as a target in various diseases. Therefore, the present review summarizes current knowledge about LCN2 in the reproductive system, including studies in rodents and humans, and discusses changes in LCN2 expression during pathological events. The limited data suggest that LCN2 is expressed and regulated differently in healthy male and female reproductive organs.
25千道尔顿大小的蛋白质lipocalin 2(LCN2)最初是30多年前从人类中性粒细胞中分离出来的。LCN2是先天性免疫防御中的一个新兴参与者,因为它能够螯合含铁的细菌铁载体,从而减少细菌生长。另一方面,由于其β桶状结构,LCN2还可作为各种疏水性物质的转运蛋白。多年来,在包括上皮细胞、星形胶质细胞和肝细胞在内的许多其他细胞类型中都检测到了LCN2。研究清楚地表明,LCN2的异常表达与多种疾病和恶性肿瘤有关,包括几种生殖系统疾病。此外,在这种情况下,LCN2被提议作为一种非侵入性的预后和/或诊断生物标志物。尽管多项研究揭示了LCN2在包括肿瘤发生在内的女性和男性生殖系统各种疾病中的作用,但对LCN2在生殖道中的生理功能仍缺乏全面了解。然而,有证据表明LCN2与生育能力直接相关,因为小鼠体内LCN2的整体缺失对其妊娠率有负面影响。由于LCN2的表达可受类固醇激素调节,因此其在女性生殖道重塑过程中,尤其是在子宫中表达波动很大也就不足为奇了。关于LCN2在健康生殖状态下的表达和调节以及生殖衰老过程中可能发生的变化的详细且有充分依据的信息,有助于更好地理解LCN2作为各种疾病靶点的作用。因此,本综述总结了目前关于LCN2在生殖系统中的知识,包括在啮齿动物和人类中的研究,并讨论了病理事件期间LCN2表达的变化。有限的数据表明,LCN2在健康的男性和女性生殖器官中的表达和调节有所不同。