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人尿中的 Tamm-Horsfall 蛋白:排泄和 N-糖基化模式的性别依赖性差异。

Tamm-Horsfall protein in humane urine: sex-dependent differences in the excretion and N-glycosylation pattern.

机构信息

Institute of Pharmaceutical Biology and Phytochemistry, University of Münster, Münster, Germany.

Organisch-Chemisches Institut, University of Münster, Münster, Germany.

出版信息

Sci Rep. 2023 Oct 19;13(1):17815. doi: 10.1038/s41598-023-44650-1.

DOI:10.1038/s41598-023-44650-1
PMID:37857738
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10587112/
Abstract

Tamm-Horsfall protein (THP) is a highly N-glycosylated protein from epithelial cells of the ascending limb of Henle loop. It is secreted into the urine as part of the innate immune response against uropathogenic pathogens. As women are more likely to suffer from urinary tract infections, biomedical studies were conducted to investigate sex-differences in THP excretion, as well as differences in the THP N-glycosylation pattern. A total of 238 volunteers (92 men, 146 women, 69 with hormonal contraceptives) participated in this study, providing urine samples. Women showed a clear tendency to have higher THP concentration and excretion rates than men (p < 0.16). Regular intake of hormonal contraceptives had no significant influence on urinary THP concentration compared to no regular intake. The individual N-glycosylation pattern of THP in urine samples from randomly selected individuals (10 female, 10 male) was investigated after enzymatic release and MS analysis of the oligosaccharides. Female subjects tended to have an increased proportion of oligomannose type N-glycans and non-fucosylated glycans, whereas men had an increased proportion of fucosylated complex-type glycans. The higher level of oligomannose-type glycans in THP from women might be explained by a self-defence mechanism to overcome the higher infections pressure by the female anatomical properties.

摘要

Tamm-Horsfall 蛋白(THP)是一种高度 N-糖基化的蛋白,来源于 Henle 袢升支的上皮细胞。它作为先天免疫反应的一部分被分泌到尿液中,以抵抗尿路致病性病原体。由于女性更容易患尿路感染,因此进行了生物医学研究,以调查 THP 排泄中的性别差异,以及 THP N-糖基化模式的差异。共有 238 名志愿者(92 名男性,146 名女性,69 名服用激素避孕药)参与了这项研究,提供了尿液样本。女性的 THP 浓度和排泄率明显高于男性(p<0.16)。与不规律服用相比,定期服用激素避孕药对尿液中 THP 浓度没有显著影响。随机选择的个体(10 名女性,10 名男性)尿液样本中的 THP 的个体 N-糖基化模式在经过酶解和 MS 分析寡糖后进行了研究。女性受试者倾向于具有增加的寡甘露糖型 N-聚糖和无岩藻糖基化聚糖的比例,而男性则具有增加的岩藻糖基化复杂型聚糖的比例。女性 THP 中寡甘露糖型聚糖水平较高可能是由于女性解剖结构导致感染压力较高,从而产生了一种自我防御机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d100/10587112/e6003cdef3ac/41598_2023_44650_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d100/10587112/0de4816d54fc/41598_2023_44650_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d100/10587112/6971a9b9f7e9/41598_2023_44650_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d100/10587112/e6003cdef3ac/41598_2023_44650_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d100/10587112/0de4816d54fc/41598_2023_44650_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d100/10587112/6971a9b9f7e9/41598_2023_44650_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d100/10587112/e6003cdef3ac/41598_2023_44650_Fig4_HTML.jpg

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