Expression and secretion of basigin by human placental trophoblast cells occurs via microvesicle shedding and is a regulated process

Ermilova, Viktoriya

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https://hdl.handle.net/2142/30925 Copy

Description

Title

Expression and secretion of basigin by human placental trophoblast cells occurs via microvesicle shedding and is a regulated process

Author(s)

Ermilova, Viktoriya

Issue Date

2012-05-22T00:15:44Z

Director of Research (if dissertation) or Advisor (if thesis)

Nowak, Romana A.

Department of Study

Animal Sciences

Discipline

Animal Sciences

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

M.S.

Degree Level

Thesis

Keyword(s)

• early placental development
• trophoblast
• basigin
• microvesicle shedding
• cytokines
• matrix metalloproteinases

Abstract

Successful pregnancy depends on the ability of trophoblast cells to invade into maternal uterine tissues in a tightly controlled manner. Subsequently the trophoblasts must remodel the uterine spiral arteries in order to establish an adequate blood supply for normal fetal and placental development. Failure of sufficient trophoblast invasion and defective remodeling of the maternal uterine spiral arteries is linked to the obstetrical disease preeclampsia. Trophoblast invasion and spiral artery remodeling are influenced by many factors such as matrix metalloproteinases (MMPs), as well as cytokines, growth factors and oxygen tension. Previous studies have demonstrated that basigin (BSG)/extracellular matrix metalloproteinase inducer (EMMPRIN) is able to regulate MMP production and is critical for successful implantation, angiogenesis and parturition. However, expression and specific functions of BSG during the first trimester of pregnancy in human placenta have not been investigated. This study focused on determining whether BSG is present in the first trimester human placenta, how secretion of BSG protein is regulated, and what the specific functions of BSG during early placentation may be. The main findings of our work are: 1) BSG protein is present in the human trophoblast throughout the first trimester of pregnancy; 2) human trophoblast-like cell lines in culture express BSG transcript variants -2, -3 and -4 and secrete BSG protein into surrounding medium; 3) release of BSG from the surface of trophoblast-like cells occurs through microvesicle shedding; 4) the signaling cascade responsible for microvesicle release is the protein kinase C (PKC) pathway; 5) BSG-containing microvesicle release by trophoblast-like cells is altered in response to hypoxia/reoxygenation injury; 6) the inflammatory cytokine interleukin-1β (IL-1β) and transforming growth factor-β1 (TGF-β1) regulate BSG protein abundance in microvesicles at the post-transcriptional level; 7) recombinant BSG protein (rBSG) stimulates release of MMP-1 and MMP-3 by cultured human umbilical vein endothelial cells (HUVECs). These findings show that BSG secretion occurs through a controlled process of microvesicle shedding in trophoblasts, and supports our hypothesis that BSG regulates interactions of trophoblast cells with other uterine cells during early placental development.

Graduation Semester

2012-05

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http://hdl.handle.net/2142/30925

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Copyright 2012 Viktoriya Ermilova

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