Parenchymal pericytes are not the major contributor of extracellular matrix in the fibrotic scar after stroke in male mice
(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.
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- 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
-
- pmid:31758600
- scopus:85075438622
- 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
- 2024-08-21 12:39:32
@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}}, }