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SCAP knockout in SM22α-Cre mice induces defective angiogenesis in the placental labyrinth

Li, Z; Li, D; Rao, Y; Wei, L; Liu, M; Zheng, G; Yao, Y; ... Ruan, XZ; + view all (2020) SCAP knockout in SM22α-Cre mice induces defective angiogenesis in the placental labyrinth. Biomedicine & Pharmacotherapy , 133 , Article 111011. 10.1016/j.biopha.2020.111011. Green open access

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Abstract

The placental labyrinth is important for the exchange of nutrients and gases between the mother and the embryo in mice. This interface contains cells of both trophoblast and allantoic mesodermal origin that together produce maternal blood sinuses and placental blood vessels. However, the molecular mechanisms that take place during process of placental labyrinth development, especially concerning fetal capillaries, are not well understood. SREBP cleavage-activating protein (SCAP), a membrane protein, is required for the synthesis of fatty acids and cholesterol. Recently, when we crossed the offspring of the cross between smooth muscle 22 alpha (SM22α)- Cre recombinase (Cre) mice and SCAPloxp/loxp mice to research the function of SCAP in vascular smooth muscle cells (VSMCs) during certain pathological processes, we found that there were no resultant SM22α-Cre-specific SCAP knockout (KO) pups (SM22α-Cre+SCAPflox/flox; hereafter referred to as SCAP KO). Through anatomic studies of these embryos and placentas, we found that SCAP KO resulted in defective placental vessels and abnormal fetal morphology. Further immunohistochemical and immunocytochemical analyses suggested that SCAP is knocked out in the pericytes of the placental labyrinth. Compared to wildtype mice, SCAP KO placentas had abnormal vasculature in the labyrinth and lower levels of angiogenesis. By using RNA-seq and western blotting, we found that the expression of some genes and proteins in SCAP KO placentas was changed, including those related to pericyte/endothelial interactions genes and angiogenesis. Our results suggest that the proper organizational structure of the placental labyrinth depends on SCAP expression in pericytes.

Type: Article
Title: SCAP knockout in SM22α-Cre mice induces defective angiogenesis in the placental labyrinth
Location: France
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.biopha.2020.111011
Publisher version: https://doi.org/10.1016/j.biopha.2020.111011
Language: English
Additional information: © 2020 The Authors. Published by Elsevier Masson SAS under a Creative Commons license (https://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: Angiogenesis, Gene expression, Pericyte, Placental labyrinth, SCAP, SM22α
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10116144
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