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RGS5 : a novel role as a hypoxia-responsive protein that suppresses chemokinetic and chemotactic migration in brain pericytes

Enström, Andreas LU orcid ; Carlsson, Robert LU ; Özen, Ilknur LU and Paul, Gesine LU (2022) In Biology Open 11(10).
Abstract

Adaptive biological mechanisms to hypoxia are crucial to maintain oxygen homeostasis, especially in the brain. Pericytes, cells uniquely positioned at the blood-brain interface, respond fast to hypoxia by expressing regulator of G-protein signalling 5 (RGS5), a negative regulator of G-protein-coupled receptors. RGS5 expression in pericytes is observed in pathological hypoxic environments (e.g. tumours and ischaemic stroke) and associated with perivascular depletion of pericytes and vessel leakage. However, the regulation of RGS5 expression and its functional role in pericytes are not known. We demonstrate that RGS5 acts as a hypoxia-responsive protein in human brain pericytes that is regulated independent of hypoxia inducible factor-1α... (More)

Adaptive biological mechanisms to hypoxia are crucial to maintain oxygen homeostasis, especially in the brain. Pericytes, cells uniquely positioned at the blood-brain interface, respond fast to hypoxia by expressing regulator of G-protein signalling 5 (RGS5), a negative regulator of G-protein-coupled receptors. RGS5 expression in pericytes is observed in pathological hypoxic environments (e.g. tumours and ischaemic stroke) and associated with perivascular depletion of pericytes and vessel leakage. However, the regulation of RGS5 expression and its functional role in pericytes are not known. We demonstrate that RGS5 acts as a hypoxia-responsive protein in human brain pericytes that is regulated independent of hypoxia inducible factor-1α (HIF-1α), rapidly stabilized under hypoxia, but degraded under normoxic conditions. We show that RGS5 expression desensitizes pericytes to signalling of platelet-derived growth factor-BB (PDGFBB) and sphingosine 1-phosphate (S1P), and blocks chemokinesis or chemotaxis induced by these factors. Our data imply a role for RGS5 in antagonizing pericyte recruitment and retention to blood vessels during hypoxia and support RGS5 as a target in counteracting vessel leakage under pathological hypoxic conditions. This article has an associated First Person interview with the first author of the paper.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Hypoxia, Migration, PDGFBB, Pericytes, RGS5, S1P
in
Biology Open
volume
11
issue
10
publisher
The Company of Biologists Ltd
external identifiers
  • scopus:85140144078
  • pmid:36111549
ISSN
2046-6390
DOI
10.1242/bio.059371
language
English
LU publication?
yes
id
51f2a5b3-2a27-4631-88e2-af8d21f7d486
date added to LUP
2022-12-13 13:05:07
date last changed
2024-06-27 22:56:51
@article{51f2a5b3-2a27-4631-88e2-af8d21f7d486,
  abstract     = {{<p>Adaptive biological mechanisms to hypoxia are crucial to maintain oxygen homeostasis, especially in the brain. Pericytes, cells uniquely positioned at the blood-brain interface, respond fast to hypoxia by expressing regulator of G-protein signalling 5 (RGS5), a negative regulator of G-protein-coupled receptors. RGS5 expression in pericytes is observed in pathological hypoxic environments (e.g. tumours and ischaemic stroke) and associated with perivascular depletion of pericytes and vessel leakage. However, the regulation of RGS5 expression and its functional role in pericytes are not known. We demonstrate that RGS5 acts as a hypoxia-responsive protein in human brain pericytes that is regulated independent of hypoxia inducible factor-1α (HIF-1α), rapidly stabilized under hypoxia, but degraded under normoxic conditions. We show that RGS5 expression desensitizes pericytes to signalling of platelet-derived growth factor-BB (PDGFBB) and sphingosine 1-phosphate (S1P), and blocks chemokinesis or chemotaxis induced by these factors. Our data imply a role for RGS5 in antagonizing pericyte recruitment and retention to blood vessels during hypoxia and support RGS5 as a target in counteracting vessel leakage under pathological hypoxic conditions. This article has an associated First Person interview with the first author of the paper.</p>}},
  author       = {{Enström, Andreas and Carlsson, Robert and Özen, Ilknur and Paul, Gesine}},
  issn         = {{2046-6390}},
  keywords     = {{Hypoxia; Migration; PDGFBB; Pericytes; RGS5; S1P}},
  language     = {{eng}},
  number       = {{10}},
  publisher    = {{The Company of Biologists Ltd}},
  series       = {{Biology Open}},
  title        = {{RGS5 : a novel role as a hypoxia-responsive protein that suppresses chemokinetic and chemotactic migration in brain pericytes}},
  url          = {{http://dx.doi.org/10.1242/bio.059371}},
  doi          = {{10.1242/bio.059371}},
  volume       = {{11}},
  year         = {{2022}},
}