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SARS-COV-2 对胎盘组织中血管生成和自噬相关分子的影响。

Effects of SARS-COV-2 on molecules involved in vascularization and autophagy in placenta tissues.

机构信息

Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy.

Laboratory for Technologies of Advanced Therapies (LTTA)-Electron Microscopy Center, University of Ferrara, Ferrara, Italy.

出版信息

J Mol Histol. 2024 Oct;55(5):753-764. doi: 10.1007/s10735-024-10228-y. Epub 2024 Aug 1.

Abstract

SARS-CoV-2 infection is considered as a multi-organ disease, and several studies highlighted the relevance of the virus infection in the induction of vascular injury and tissue morphological alterations, including placenta. In this study, immunohistochemical analyses were carried out on placenta samples derived from women with COVID-19 infection at delivery (SARS-CoV-2 PCR+) or women healed from a COVID-19 infection (SARS-CoV-2 negative at delivery, SARS-CoV-2 PCR-) or women who gave birth before 2019 (Control). Angiotensin Converting Enzyme 2 (ACE2) receptor, Cluster of differentiation 147 (CD147), endothelial CD34 marker, Vascular Endothelial Growth Factor (VEGF) and total Microtubule-associated protein 1 Light Chain 3B marker (LC3B) were investigated in parallel with SPIKE protein by standard IHC. Multiplexed Immunohistochemical Consecutive Staining on Single Slide (MICSSS) was used to examine antigen co-expression in the same specimen. SPIKE protein was detected in villi and decidua from women with ongoing infection, with no significant differences in SPIKE staining between both biopsy sites. VEGF was significantly increased in SARS-CoV-2 PCR + biopsies compared to control and SARS-CoV-2 PCR- samples, and MICSSS method showed the co-localization of SPIKE with VEGF and CD34. The induction of autophagy, as suggested by the LC3B increase in SARS-CoV-2 PCR + biopsies and the co-expression of LC3B with SPIKE protein, may explain one of the different mechanisms by which placenta may react to infection. These data could provide important information on the impact that SARS-CoV-2 may have on the placenta and mother-to-fetus transmission.

摘要

SARS-CoV-2 感染被认为是一种多器官疾病,多项研究强调了病毒感染在诱导血管损伤和组织形态改变中的相关性,包括胎盘。在这项研究中,对来自分娩时 COVID-19 感染(SARS-CoV-2 PCR+)或从 COVID-19 感染中康复的女性(分娩时 SARS-CoV-2 阴性,SARS-CoV-2 PCR-)或在 2019 年前分娩的女性(对照组)的胎盘样本进行了免疫组织化学分析。并行研究了血管紧张素转换酶 2(ACE2)受体、分化簇 147(CD147)、内皮 CD34 标志物、血管内皮生长因子(VEGF)和总微管相关蛋白 1 轻链 3B 标志物(LC3B)以及 SPIKE 蛋白。采用单幻灯片上的多重免疫组织化学连续染色(MICSSS)方法在同一标本中检测抗原共表达。在持续感染的女性的绒毛和蜕膜中检测到 SPIKE 蛋白,SPIKE 染色在两个活检部位之间没有显著差异。与对照组和 SARS-CoV-2 PCR- 样本相比,SARS-CoV-2 PCR+ 活检中的 VEGF 显著增加,并且 MICSSS 方法显示 SPIKE 与 VEGF 和 CD34 的共定位。LC3B 的增加提示自噬的诱导,SARS-CoV-2 PCR+ 活检中 LC3B 的共表达以及 SPIKE 蛋白,可能解释了胎盘对感染可能产生不同反应的机制之一。这些数据可为 SARS-CoV-2 对胎盘和母婴传播可能产生的影响提供重要信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a659/11464539/6f2441f82c9a/10735_2024_10228_Fig1_HTML.jpg

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