Title

The Relationship of ADAMTS1 and ANGPT2 with Reelin in Vascular Endothelial Cells

Date of Award

5-2022

Degree Type

Thesis

Degree Name

Master of Science in Biomedical Sciences

First Advisor

Cathy J. Hatcher, PhD

Second Advisor

Ruth C. Borghaei, PhD

Third Advisor

Jocelyn Lippman-Bell, PhD

Abstract

The formation of coronary vessels is fundamental in heart development. The Hatcher lab has demonstrated that Reelin, an extracellular matrix glycoprotein, is involved in the formation of coronary vessels. Reelin expression is localized to the vascular endothelial cells of coronary vessels in embryonic mice. Human dermal microvascular endothelial cells (HDMECs) were used to examine the potential role of Reelin in vascular development as they appropriately model events involved in vessel formation and have endogenous expression of RELN mRNA. Previous studies from our lab indicated that small interfering RNA (siRNA)-mediated gene silencing of RELN in HDMECs reduced cell migration and basal cell membrane permeability, and increased capillary-like tube formation. Based on these results, we believe Reelin is involved in vasculogenesis and angiogenesis. This prompted us to analyze expression of angiogenic transcripts by qPCR array in negative control and RELN knockdown (KD) HDMECs. Our current study shows that ANGPT2 mRNA and protein expression was not altered in RELN KD cells. However, there is a significant upregulation of ADAMTS1 mRNA and protein expression in RELN KD vascular endothelial cells compared to control cells. In addition, ADAMTS1 is found on the nucleus of these cells where it may exhibit proteolytic functions. Based on these findings, we conclude that ADAMTS1 is a potential downstream effector of Reelin signaling and contributes to vascular endothelial cell functions that are important for vessel formation.

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