Parenchymal pericytes are not the major contributor of extracellular matrix in the fibrotic scar after stroke in male mice
Roth, Michaela LU ; Enström, Andreas LU
; Aghabeick, Candice
; Carlsson, Robert
LU
; Genové, Guillem
and Paul, Gesine
LU
(2020)
In Journal of Neuroscience Research
98(5).
p.826-842
- Abstract
Scar formation after injury of the brain or spinal cord is a common event. While glial scar formation by astrocytes has been extensively studied, much less is known about the fibrotic scar, in particular after stroke. Platelet-derived growth factor receptor ß-expressing (PDGFRß+) pericytes have been suggested as a source of the fibrotic scar depositing fibrous extracellular matrix (ECM) proteins after detaching from the vessel wall. However, to what extent these parenchymal PDGFRß+ cells contribute to the fibrotic scar and whether targeting these cells affects fibrotic scar formation in stroke is still unclear. Here, we utilize male transgenic mice that after a permanent middle cerebral artery occlusion stroke... (More)
Scar formation after injury of the brain or spinal cord is a common event. While glial scar formation by astrocytes has been extensively studied, much less is known about the fibrotic scar, in particular after stroke. Platelet-derived growth factor receptor ß-expressing (PDGFRß+) pericytes have been suggested as a source of the fibrotic scar depositing fibrous extracellular matrix (ECM) proteins after detaching from the vessel wall. However, to what extent these parenchymal PDGFRß+ cells contribute to the fibrotic scar and whether targeting these cells affects fibrotic scar formation in stroke is still unclear. Here, we utilize male transgenic mice that after a permanent middle cerebral artery occlusion stroke model have a shift from a parenchymal to a perivascular location of PDGFRß+ cells due to the loss of regulator of G-protein signaling 5 in pericytes. We find that only a small fraction of parenchymal PDGFRß+ cells co-label with type I collagen and fibronectin. Consequently, a reduction in parenchymal PDGFRß+ cells by ca. 50% did not affect the overall type I collagen or fibronectin deposition after stroke. The redistribution of PDGFRß+ cells to a perivascular location, however, resulted in a reduced thickening of the vascular basement membrane and changed the temporal dynamics of glial scar maturation after stroke. We demonstrate that parenchymal PDGFRß+ cells are not the main contributor to the fibrotic ECM, and therefore targeting these cells might not impact on fibrotic scar formation after stroke.
(Less)
- author
- Roth, Michaela
LU
; Enström, Andreas
LU
; Aghabeick, Candice
; Carlsson, Robert
LU
; Genové, Guillem
and Paul, Gesine
LU
- organization
- publishing date
- 2020-05
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- collagen, extracellular matrix, fibronectin, fibrotic scar, glial scar, pericytes, RRID:AB_2082660, RRID:AB_2105706, RRID:AB_2162497, RRID:AB_217595, RRID:AB_2298772, RRID:AB_298179, RRID:AB_305808, RRID:AB_354858, RRID:AB_393571, RRID:AB_467492, RRID:SCR_002798, RRID:SCR_003070, RRID:SCR_010279, stroke
- in
- Journal of Neuroscience Research
- volume
- 98
- issue
- 5
- pages
- 17 pages
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- scopus:85075438622
- pmid:31758600
- ISSN
- 0360-4012
- DOI
- 10.1002/jnr.24557
- language
- English
- LU publication?
- yes
- id
- d2fd9fb0-5581-4d09-a08c-d1de7e86b0a0
- date added to LUP
- 2019-12-09 10:21:30
- date last changed
- 2025-10-14 09:20:58
@article{d2fd9fb0-5581-4d09-a08c-d1de7e86b0a0,
abstract = {{<p>Scar formation after injury of the brain or spinal cord is a common event. While glial scar formation by astrocytes has been extensively studied, much less is known about the fibrotic scar, in particular after stroke. Platelet-derived growth factor receptor ß-expressing (PDGFRß<sup>+</sup>) pericytes have been suggested as a source of the fibrotic scar depositing fibrous extracellular matrix (ECM) proteins after detaching from the vessel wall. However, to what extent these parenchymal PDGFRß<sup>+</sup> cells contribute to the fibrotic scar and whether targeting these cells affects fibrotic scar formation in stroke is still unclear. Here, we utilize male transgenic mice that after a permanent middle cerebral artery occlusion stroke model have a shift from a parenchymal to a perivascular location of PDGFRß<sup>+</sup> cells due to the loss of regulator of G-protein signaling 5 in pericytes. We find that only a small fraction of parenchymal PDGFRß<sup>+</sup> cells co-label with type I collagen and fibronectin. Consequently, a reduction in parenchymal PDGFRß<sup>+</sup> cells by ca. 50% did not affect the overall type I collagen or fibronectin deposition after stroke. The redistribution of PDGFRß<sup>+</sup> cells to a perivascular location, however, resulted in a reduced thickening of the vascular basement membrane and changed the temporal dynamics of glial scar maturation after stroke. We demonstrate that parenchymal PDGFRß<sup>+</sup> cells are not the main contributor to the fibrotic ECM, and therefore targeting these cells might not impact on fibrotic scar formation after stroke.</p>}},
author = {{Roth, Michaela and Enström, Andreas and Aghabeick, Candice and Carlsson, Robert and Genové, Guillem and Paul, Gesine}},
issn = {{0360-4012}},
keywords = {{collagen; extracellular matrix; fibronectin; fibrotic scar; glial scar; pericytes; RRID:AB_2082660; RRID:AB_2105706; RRID:AB_2162497; RRID:AB_217595; RRID:AB_2298772; RRID:AB_298179; RRID:AB_305808; RRID:AB_354858; RRID:AB_393571; RRID:AB_467492; RRID:SCR_002798; RRID:SCR_003070; RRID:SCR_010279; stroke}},
language = {{eng}},
number = {{5}},
pages = {{826--842}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Journal of Neuroscience Research}},
title = {{Parenchymal pericytes are not the major contributor of extracellular matrix in the fibrotic scar after stroke in male mice}},
url = {{http://dx.doi.org/10.1002/jnr.24557}},
doi = {{10.1002/jnr.24557}},
volume = {{98}},
year = {{2020}},
}