Schwann cell migration is integrin-dependent and inhibited by astrocyte-produced aggrecan

Afshari, Fardad T.; Kwok, Jessica C.; White, Linda; Fawcett, James W.

doi:10.1002/glia.20970

Cited by 103Nerve injury and regenerationProteoglycans and glycosaminoglycans researchSpinal Cord Injury Research

Schwann cell migration is integrin-dependent and inhibited by astrocyte-produced aggrecan

Afshari, Fardad T., Kwok, Jessica C., White, Linda, Fawcett, James W.·2010·Glia

DOI 10.1002/glia.20970

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Abstract

Schwann cells transplantation has considerable promise in spinal cord trauma to bridge the site of injury and for remyelination in demyelinating conditions. They support axonal regeneration and sprouting by secreting growth factors and providing a permissive surface and matrix molecules while shielding axons from the inhibitory environment of the central nervous system. However, following transplantation Schwann cells show limited migratory ability and they are unable to intermingle with the host astrocytes. This in turn leads to formation of a sharp boundary and an abrupt transition between the Schwann cell graft and the host tissue astrocytes, therefore preventing regenerating axons from exiting the graft. The objective of this study was to identify inhibitory elements on astrocytes involved in restricting Schwann cell migration. Using in vitro assays of cell migration, we show that aggrecan produced by astrocytes is involved in the inhibition of Schwann cell motility on astrocytic monolayers. Knockdown of this proteoglycan in astrocytes using RNAi or digestion of glycosaminglycan chains on aggrecan improves Schwann cell migration. We further show aggrecan mediates its effect by disruption of integrin function in Schwann cells, and that the inhibitory effects of aggrecan can overcome by activation of Schwann cell integrins. © 2010 Wiley‐Liss, Inc.

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CSPGs, especially their GAG moieties, may inhibit growth by blocking the growth-promoting activity of integrins.
“Specifically, CSPGs, and particularly their GAG moieties, may act by i) binding to a specific receptor; ii) blocking the growth-promoting activity of integrins; iii) presenting growth-inhibitory proteins.”
From The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015) · cites this paper as Afshari et al., 2010
Reduced integrin activation occurs in neurons cultured on CSPG-coated substrate, which show growth inhibition; CSPG digestion releases the negative effects of CSPG on integrin activation and neurite outgrowth.
“Reduced integrin activation is present in neurons cultured on substrate coated with CSPGs, which display growth inhibition and CSPG digestion release the negative effects of CSPG on integrin activation and neurite outgrowth (Afshari et al., 2010).”
From The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity (2015) · cites this paper as Afshari et al., 2010

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Authors: Afshari, F. T., Kwok, J. C., White, L., & Fawcett, J. W.
Affiliations: University of Cambridge (GB)
University of Miami (US)
Corresponding author: Fawcett, James W.
ORCID: Afshari, Fardad T.
Kwok, Jessica C.
Fawcett, James W.
Venue: Glia
Publisher: Wiley
Published: 2010-02-12
Volume: 58
Issue: 7
Pages: 857-869
ISSN: 0894-1491 (ISSN-L)
1098-1136
DOI: 10.1002/glia.20970
OpenAlex: W1971817487
Cited by: 103
References: 62
Citations by year: 2026: 2 · 2025: 1 · 2024: 2 · 2023: 5 · 2022: 3 · 2021: 4 · 2020: 5 · 2019: 1 · 2018: 3 · 2017: 9 · 2016: 12 · 2015: 10 · 2014: 12 · 2013: 9 · 2012: 10
FWCI: 4.40
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Glia (publishedVersion)
PubMed (publishedVersion)
Funders: University of Miami
Wellcome Trust
Leonard M. Miller School of Medicine
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
Keywords: Schwann cell migration, aggrecan, astrocytes, integrins, Schwann cell transplantation, spinal cord injury, remyelination, axon regeneration, proteoglycans, glycosaminoglycans, cell migration inhibition
MeSH terms: Animals, Animals, Newborn, Astrocytes, Cell Communication, Cell Movement, Cells, Cultured, Extracellular Matrix, Glycosaminoglycans, Graft Survival, Humans, Schwann Cells, Down-Regulation, Integrins, Tissue Transplantation, Rats, Sprague-Dawley, RNA Interference, Rats, Aggrecans

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Schwann cell migration is integrin-dependent and inhibited by astrocyte-produced aggrecan

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