Skip to main content

LUP Student Papers

LUND UNIVERSITY LIBRARIES

Regulator of G-protein Signaling 5 Regulates Human Brain Vascular Pericyte Migration

Enström, Andreas (2018) MOBN01 20171
Degree Projects in Molecular Biology
Popular Abstract
Cellular Migration: Natures compass to preserve the Blood-Brain–Barrier

The Blood-Brain-Barrier (BBB) is a specialized and essential structure to ensure optimal physiological conditions in the brain. It separates the circulating blood and its components from sensitive neurons in the brain limiting and selecting which constituents that are transported from blood to brain and vice versa. Pericytes are a relative newcomer in the field of vascular biology but are key components in smaller vessels like capillaries. They are migratory cells and vessels are dependent on recruiting pericytes that envelop and establish an intact microvasculature including the BBB. Other than satisfying the energy, oxygen and metabolic demand of the brain under... (More)
Cellular Migration: Natures compass to preserve the Blood-Brain–Barrier

The Blood-Brain-Barrier (BBB) is a specialized and essential structure to ensure optimal physiological conditions in the brain. It separates the circulating blood and its components from sensitive neurons in the brain limiting and selecting which constituents that are transported from blood to brain and vice versa. Pericytes are a relative newcomer in the field of vascular biology but are key components in smaller vessels like capillaries. They are migratory cells and vessels are dependent on recruiting pericytes that envelop and establish an intact microvasculature including the BBB. Other than satisfying the energy, oxygen and metabolic demand of the brain under physiological conditions, certain pathologies like stroke and tumor progression are also reliant on vessel formation. Thus, accumulating evidence points to a role of pericytes in disease. During these events of vascular commotion pericytes become activated and express high levels of Regulator of G-protein signaling 5 (RGS5) serving as a possible link to pericyte fate under these conditions.

RGS5 regulates G-Protein Coupled Receptors, which are abundantly expressed in the human body and functions much like an ON/OFF switch of their intracellular signaling pathways. Although the mechanism of RGS5 have been well studied, much still remains to be clarified in terms of its physiological role. Here we proposed RGS5 as a regulator of pericyte migration and subsequently their recruitment to the vascular wall.

We used a cell culture model of human brain vascular pericytes to identify their migrational properties when reducing or inducing the intracellular levels of RGS5. Live imaging microscopy was used to analyse the cellular mobility in real-time. After confirmation of RGS5´s regulatory role in cell mobility, key molecular techniques were used to dissect the signalling pathway of RGS5 looking at their gene expression, protein levels and their distribution.
Loss of RGS5 induce Pericyte Migration
Reducing the amount of available RGS5 in pericytes increased their migration capabilities substantially. This observation was also associated with changes in cellular shape necessary for mobility. Loss of RGS5 induced cellular branching and extensions that could attach and retract as cells moved along the surface. Furthermore, we identified two signalling pathways that may be active in the absence of RGS5 and important in initiating and maintaining cellular migration.

In the BBB, cell-cell interactions between neurons, vascular cells such as endothelial cells and pericytes maintain brain homeostasis. Understanding pericyte migration and the mechanisms behind it gives us an important insight in how the microvasculature in the brain is regulated and opens up opportunities to control these functions and effect secondary changes leading to brain damage or repair. Meanwhile, vessel formation is naturally extremely important during development but also continues in adults. Finding regulatory mechanisms can give us valuable tools in regulating the integrity and development of sprouting vessels accordingly, depending on the circumstances. Our study supports that RGS5 may be a key player in regulating such mechanisms.

Master’s Degree Project in Molecular Biology/Molecular Genetics/Biotechnology, credits 45
Department of Biology, Lund University
Supervisor: Ilknur Özen
Translational Neurology, Faculty of Medicine, Lund University (Less)
Please use this url to cite or link to this publication:
author
Enström, Andreas
supervisor
organization
course
MOBN01 20171
year
type
H2 - Master's Degree (Two Years)
subject
language
English
id
8938040
date added to LUP
2018-03-26 11:16:02
date last changed
2018-03-26 11:16:02
@misc{8938040,
  author       = {{Enström, Andreas}},
  language     = {{eng}},
  note         = {{Student Paper}},
  title        = {{Regulator of G-protein Signaling 5 Regulates Human Brain Vascular Pericyte Migration}},
  year         = {{2018}},
}