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波形蛋白作为新冠病毒感染病例尸检睾丸组织中新冠病毒诱导睾丸炎的一个促成因素:一项病例对照研究

Vimentin as a contributing factor in SARS-CoV-2-induced orchitis on postmortem testicular autopsy of COVID-19 cases: A case-control study.

作者信息

Akaberi-Nasrabadi Soheila, Sabbaghi Azam, M Toosi Behzad, Ghorbanifaraz Parsa, Mahmoudiasl Gholam-Reza, Aliaghaei Abbas, Faghihi Hosseinabadi Hajarsadat, Paktinat Shahrokh, Abdollahifar Mohammad-Amin

机构信息

Urology and Nephrology Research Center, Research Institute for Urology and Nephrology, Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran.

Department of Small Animal Clinical Sciences, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.

出版信息

Int J Reprod Biomed. 2024 Jan 10;22(11):895-906. doi: 10.18502/ijrm.v22i11.17822. eCollection 2024 Nov.

DOI:10.18502/ijrm.v22i11.17822
PMID:39866583
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11757669/
Abstract

BACKGROUND

Coronavirus disease 2019 (COVID-19) was identified in China in late December 2019 and led to a pandemic that resulted in millions of confirmed cases and deaths. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), uses distinct receptors and co-receptors to enter host cells. Vimentin has emerged as a potential co-receptor for SARS-CoV-2 due to the high level of vimentin expression in testis tissue.

OBJECTIVE

The present study investigated the link between vimentin expression level and SARS-CoV-2-induced orchitis.

MATERIALS AND METHODS

In this case-control study, testis autopsy samples were collected immediately after the death of both COVID-19 cases and a control group that included individuals who died due to accidental causes. Gene expression and immunohistochemical assays were conducted to evaluate the level of vimentin expression, cell proliferation, and leukocyte infiltration.

RESULTS

A significant expression of vimentin and infiltration of immune cells (CD68+, CD38+, and CD138+) in the testicular tissue of COVID-19 cases, along with extensive immunoglobulin G precipitation and reduced inhibin expression (p = 0.001) were observed. Additionally, gene expression analysis revealed increased expression of vimentin and decreased expression of the proliferation markers Ki67 and proliferating cell nuclear antigen, suggesting that SARS-CoV-2 may disrupt spermatogenesis through immune responses and the arrest of cell proliferation.

CONCLUSION

There may be a strong link between vimentin expression and COVID-19-induced orchitis. Further studies are needed to confirm these findings. Considering some limitations, vimentin can be used as a biomarker option for testicular damage following COVID-19-induced orchitis.

摘要

背景

2019年12月下旬在中国发现了2019冠状病毒病(COVID-19),并引发了一场大流行,导致数百万确诊病例和死亡。病原体严重急性呼吸综合征冠状病毒2(SARS-CoV-2)利用不同的受体和共受体进入宿主细胞。波形蛋白已成为SARS-CoV-2的潜在共受体,因为睾丸组织中波形蛋白表达水平较高。

目的

本研究调查波形蛋白表达水平与SARS-CoV-2诱导的睾丸炎之间的联系。

材料与方法

在这项病例对照研究中,在COVID-19病例以及包括因意外原因死亡的个体的对照组死亡后立即收集睾丸尸检样本。进行基因表达和免疫组织化学分析以评估波形蛋白表达水平、细胞增殖和白细胞浸润。

结果

观察到COVID-19病例的睾丸组织中波形蛋白的显著表达以及免疫细胞(CD68 +、CD38 +和CD138 +)的浸润,同时伴有广泛的免疫球蛋白G沉淀和抑制素表达降低(p = 0.001)。此外,基因表达分析显示波形蛋白表达增加,增殖标志物Ki67和增殖细胞核抗原表达降低,这表明SARS-CoV-2可能通过免疫反应和细胞增殖停滞破坏精子发生。

结论

波形蛋白表达与COVID-19诱导的睾丸炎之间可能存在密切联系。需要进一步研究来证实这些发现。考虑到一些局限性,波形蛋白可作为COVID-19诱导的睾丸炎后睾丸损伤的生物标志物选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f64/11757669/779af365cead/ijrb-22-895-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f64/11757669/70178bd1a53b/ijrb-22-895-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f64/11757669/b030d4374455/ijrb-22-895-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f64/11757669/279c5b5fed17/ijrb-22-895-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f64/11757669/779af365cead/ijrb-22-895-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f64/11757669/70178bd1a53b/ijrb-22-895-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f64/11757669/b030d4374455/ijrb-22-895-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f64/11757669/279c5b5fed17/ijrb-22-895-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f64/11757669/779af365cead/ijrb-22-895-g004.jpg

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本文引用的文献

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Vimentin cage - A double-edged sword in host anti-infection defense.波形蛋白笼——宿主抗感染防御中的双刃剑。
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Vimentin takes a hike - Emerging roles of extracellular vimentin in cancer and wound healing.波形蛋白出走——细胞外波形蛋白在癌症和创伤愈合中的新作用。
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Vimentin: from a cytoskeletal protein to a critical modulator of immune response and a target for infection.
波形蛋白:从细胞骨架蛋白到免疫反应的关键调节剂和感染靶点。
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COVID-19 disrupts the blood-testis barrier through the induction of inflammatory cytokines and disruption of junctional proteins.COVID-19 通过诱导炎症细胞因子和破坏连接蛋白破坏血睾屏障。
Inflamm Res. 2021 Dec;70(10-12):1165-1175. doi: 10.1007/s00011-021-01497-4. Epub 2021 Aug 26.
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Role of Extracellular Vimentin in Cancer-Cell Functionality and Its Influence on Cell Monolayer Permeability Changes Induced by SARS-CoV-2 Receptor Binding Domain.细胞外波形蛋白在癌细胞功能中的作用及其对 SARS-CoV-2 受体结合域诱导的细胞单层通透性变化的影响。
Int J Mol Sci. 2021 Jul 12;22(14):7469. doi: 10.3390/ijms22147469.
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Testicular pathology in fatal COVID-19: A descriptive autopsy study.COVID-19 相关死亡病例的睾丸病理学表现:一项尸检描述性研究。
Andrology. 2022 Jan;10(1):13-23. doi: 10.1111/andr.13073. Epub 2021 Jul 16.
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