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孕激素受体膜组份 1 可能促进阿尔茨海默病患者人脑微血管内皮细胞的存活。

Progesterone Receptor Membrane Component-1 May Promote Survival of Human Brain Microvascular Endothelial Cells in Alzheimer's Disease.

机构信息

Department of Gynecological Endocrinology, 105762Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China; Beijing Maternal and Child Health Care Hospital, Beijing, China.

Research Centre for Women's Health and University Women's Hospital of Tuebingen, University of Tuebingen, Tuebingen, Germany.

出版信息

Am J Alzheimers Dis Other Demen. 2022 Jan-Dec;37:15333175221109749. doi: 10.1177/15333175221109749.

Abstract

Cerebrovascular changes occur in Alzheimer's disease (AD). The progesterone receptor membrane component-1 (PGRMC1) is a well identified hormone receptor with multiple functions in AD. This study aims to explore the involvement of PGRMC1 in the regulation of vascular endothelial function, providing new therapy options for AD. Single-cell sequencing revealed that the expression of PGRMC1 is lower in AD. By bioinformatics analysis, we found PGRMC1 was associated with regulation of cell proliferation, angiogenesis and etc. To understand the functional significance of PGRMC1, knockdown and overexpression were performed using human brain microvascular endothelial cells (HBMVECs), respectively. Cell proliferation assay, migration assay, tube formation assay were performed in experiments. We demonstrated that the overexpression of PGRMC1 promoted the cellular processes associated with endothelia cell proliferation, migration, and angiogenesis, significantly. In conclusion, PGRMC1 may contribute to the modulation of HBMVECs function in AD. This finding may offer novel targets for AD treatment.

摘要

阿尔茨海默病(AD)会发生脑血管变化。孕激素受体膜成分 1(PGRMC1)是一种已被充分鉴定的激素受体,在 AD 中有多种功能。本研究旨在探讨 PGRMC1 在血管内皮功能调节中的作用,为 AD 提供新的治疗选择。单细胞测序显示 AD 中 PGRMC1 的表达水平较低。通过生物信息学分析,我们发现 PGRMC1 与细胞增殖、血管生成等的调节有关。为了了解 PGRMC1 的功能意义,我们分别使用人脑血管内皮细胞(HBMVECs)进行了敲低和过表达实验。在实验中进行了细胞增殖试验、迁移试验和管形成试验。我们证明 PGRMC1 的过表达显著促进了内皮细胞增殖、迁移和血管生成等相关的细胞过程。总之,PGRMC1 可能有助于调节 AD 中的 HBMVECs 功能。这一发现可能为 AD 的治疗提供新的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b603/10581101/31e2aecc9dea/10.1177_15333175221109749-fig1.jpg

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