RGS5: a novel role as a hypoxia-responsive protein that suppresses chemokinetic and chemotactic migration in brain pericytes
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-couple...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2022-10-01
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| Series: | Biology Open |
| Subjects: | |
| Online Access: | http://bio.biologists.org/content/11/10/bio059371 |
| _version_ | 1798022535113080832 |
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| author | Andreas Enström Robert Carlsson Ilknur Özen Gesine Paul |
| author_facet | Andreas Enström Robert Carlsson Ilknur Özen Gesine Paul |
| author_sort | Andreas Enström |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T17:31:34Z |
| format | Article |
| id | doaj.art-cb8e8f8dc24f48afb3236373a20f561a |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-04-11T17:31:34Z |
| publishDate | 2022-10-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-cb8e8f8dc24f48afb3236373a20f561a2022-12-22T04:12:00ZengThe Company of BiologistsBiology Open2046-63902022-10-01111010.1242/bio.059371059371RGS5: a novel role as a hypoxia-responsive protein that suppresses chemokinetic and chemotactic migration in brain pericytesAndreas Enström0Robert Carlsson1Ilknur Özen2Gesine Paul3 Translational Neurology Group, Department of Clinical Science, Lund University, Lund 221 84, Sweden Translational Neurology Group, Department of Clinical Science, Lund University, Lund 221 84, Sweden Translational Neurology Group, Department of Clinical Science, Lund University, Lund 221 84, Sweden Translational Neurology Group, Department of Clinical Science, Lund University, Lund 221 84, Sweden 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.http://bio.biologists.org/content/11/10/bio059371hypoxiamigrationpdgfbbpericytesrgs5s1p |
| spellingShingle | Andreas Enström Robert Carlsson Ilknur Özen Gesine Paul RGS5: a novel role as a hypoxia-responsive protein that suppresses chemokinetic and chemotactic migration in brain pericytes Biology Open hypoxia migration pdgfbb pericytes rgs5 s1p |
| title | RGS5: a novel role as a hypoxia-responsive protein that suppresses chemokinetic and chemotactic migration in brain pericytes |
| title_full | RGS5: a novel role as a hypoxia-responsive protein that suppresses chemokinetic and chemotactic migration in brain pericytes |
| title_fullStr | RGS5: a novel role as a hypoxia-responsive protein that suppresses chemokinetic and chemotactic migration in brain pericytes |
| title_full_unstemmed | RGS5: a novel role as a hypoxia-responsive protein that suppresses chemokinetic and chemotactic migration in brain pericytes |
| title_short | RGS5: a novel role as a hypoxia-responsive protein that suppresses chemokinetic and chemotactic migration in brain pericytes |
| title_sort | rgs5 a novel role as a hypoxia responsive protein that suppresses chemokinetic and chemotactic migration in brain pericytes |
| topic | hypoxia migration pdgfbb pericytes rgs5 s1p |
| url | http://bio.biologists.org/content/11/10/bio059371 |
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