Dataset Information

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

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.

SUBMITTER: Xu X

PROVIDER: S-EPMC10581101 | biostudies-literature | 2022 Jan-Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Xu Xin X Ruan Xiangyan X Ju Rui R Wang Zhikun Z Yang Yu Y Cheng Jiaojiao J Gu Muqing M Mueck Alfred O AO

American journal of Alzheimer's disease and other dementias 20220101

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 proliferatio ...[more]

PMID: 35730360

Similar Datasets

Project description:BackgroundDecidualization of endometrial cells is the prerequisite for embryo implantation and subsequent placenta formation and is induced by rising progesterone levels following ovulation. One of the hormone receptors contributing to endometrial homeostasis is Progesterone Receptor Membrane Component 1 (PGRMC1), a non-classical membrane-bound progesterone receptor with yet unclear function. In this study, we aimed to investigate how PGRMC1 contributes to human decidualization.MethodsWe first analyzed PGRMC1 expression profile during a regular menstrual cycle in RNA-sequencing datasets. To further explore the function of PGRMC1 in human decidualization, we implemented an inducible decidualization system, which is achieved by culturing two human endometrial stromal cell lines in decidualization-inducing medium containing medroxyprogesterone acetate and 8-Br-cAMP. In our system, we measured PGRMC1 expression during hormone induction as well as decidualization status upon PGRMC1 knockdown at different time points. We further conferred proximity ligation assay to identify PGRMC1 interaction partners.ResultsIn a regular menstrual cycle, PGRMC1 mRNA expression is gradually decreased from the proliferative phase to the secretory phase. In in vitro experiments, we observed that PGRMC1 expression follows a rise-to-decline pattern, in which its expression level initially increased during the first 6 days after induction (PGRMC1 increasing phase) and decreased in the following days (PGRMC1 decreasing phase). Knockdown of PGRMC1 expression before the induction led to a failed decidualization, while its knockdown after induction did not inhibit decidualization, suggesting that the progestin-induced 'PGRMC1 increasing phase' is essential for normal decidualization. Furthermore, we found that the interactions of prohibitin 1 and prohibitin 2 with PGRMC1 were induced upon progestin treatment. Knocking down each of the prohibitins slowed down the decidualization process compared to the control, suggesting that PGRMC1 cooperates with prohibitins to regulate decidualization.ConclusionsAccording to our findings, PGRMC1 expression followed a progestin-induced rise-to-decline expression pattern during human endometrial decidualization process; and the correct execution of this expression program was crucial for successful decidualization. Thereby, the results of our in vitro model explained how PGRMC1 dysregulation during decidualization may present a new perspective on infertility-related diseases.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets