Different Functions of Recombinantly Expressed Domains of Tenascin-C in Glial Scar Formation
2021
Authors
Bijelić, DunjaAdžić, Marija
Perić, Mina
Jakovcevski, Igor
Foerster, Eckart
Schachner, Melitta
Andjus, Pavle R.
Article (Published version)
Metadata
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Extracellular matrix glycoprotein tenascin-C (TnC) is highly expressed in vertebrates during embryonic development and thereafter transiently in tissue niches undergoing extensive remodeling during regeneration after injury. TnC's different functions can be attributed to its multimodular structure represented by distinct domains and alternatively spliced isoforms. Upon central nervous system injury, TnC is upregulated and secreted into the extracellular matrix mainly by astrocytes. The goal of the present study was to elucidate the role of different TnC domains in events that take place after spinal cord injury (SCI). Astrocyte cultures prepared from TnC-deficient (TnC-/-) and wild-type (TnC+/+) mice were scratched and treated with different recombinantly generated TnC fragments. Gap closure, cell proliferation and expression of GFAP and cytokines were determined in these cultures. Gap closure in vitro was found to be delayed by TnC fragments, an effect mainly mediated by decreasing pr...oliferation of astrocytes. The most potent effects were observed with fragments FnD, FnA and their combination. TnC-/- astrocyte cultures exhibited higher GFAP protein and mRNA expression levels, regardless of the type of fragment used for treatment. Application of TnC fragments induced also pro-inflammatory cytokine production by astrocytes in vitro. In vivo, however, the addition of FnD or Fn(D+A) led to a difference between the two genotypes, with higher levels of GFAP expression in TnC+/+ mice. FnD treatment of injured TnC-/- mice increased the density of activated microglia/macrophages in the injury region, while overall cell proliferation in the injury site was not affected. We suggest that altogether these results may explain how the reaction of astrocytes is delayed while their localization is restricted to the border of the injury site to allow microglia/macrophages to form a lesion core during the first stages of glial scar formation, as mediated by TnC and, in particular, the alternatively spliced FnD domain.
Keywords:
tenascin-C / spinal cord injury / microglia / macrophages / glial scar / astrocyteSource:
Frontiers in Immunology, 2021, 11Publisher:
- Frontiers Media Sa, Lausanne
Funding / projects:
- DAAD/MESTD project "Involvement of Tenascin-C in Astrocyte Scarring After Spinal Cord Injury" [451-03-01766/2014-09/6]
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200178 (University of Belgrade, Faculty of Biology) (RS-MESTD-inst-2020-200178)
DOI: 10.3389/fimmu.2020.624612
ISSN: 1664-3224
PubMed: 33679718
WoS: 000625460100001
Scopus: 2-s2.0-85102294800
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Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Bijelić, Dunja AU - Adžić, Marija AU - Perić, Mina AU - Jakovcevski, Igor AU - Foerster, Eckart AU - Schachner, Melitta AU - Andjus, Pavle R. PY - 2021 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/1462 AB - Extracellular matrix glycoprotein tenascin-C (TnC) is highly expressed in vertebrates during embryonic development and thereafter transiently in tissue niches undergoing extensive remodeling during regeneration after injury. TnC's different functions can be attributed to its multimodular structure represented by distinct domains and alternatively spliced isoforms. Upon central nervous system injury, TnC is upregulated and secreted into the extracellular matrix mainly by astrocytes. The goal of the present study was to elucidate the role of different TnC domains in events that take place after spinal cord injury (SCI). Astrocyte cultures prepared from TnC-deficient (TnC-/-) and wild-type (TnC+/+) mice were scratched and treated with different recombinantly generated TnC fragments. Gap closure, cell proliferation and expression of GFAP and cytokines were determined in these cultures. Gap closure in vitro was found to be delayed by TnC fragments, an effect mainly mediated by decreasing proliferation of astrocytes. The most potent effects were observed with fragments FnD, FnA and their combination. TnC-/- astrocyte cultures exhibited higher GFAP protein and mRNA expression levels, regardless of the type of fragment used for treatment. Application of TnC fragments induced also pro-inflammatory cytokine production by astrocytes in vitro. In vivo, however, the addition of FnD or Fn(D+A) led to a difference between the two genotypes, with higher levels of GFAP expression in TnC+/+ mice. FnD treatment of injured TnC-/- mice increased the density of activated microglia/macrophages in the injury region, while overall cell proliferation in the injury site was not affected. We suggest that altogether these results may explain how the reaction of astrocytes is delayed while their localization is restricted to the border of the injury site to allow microglia/macrophages to form a lesion core during the first stages of glial scar formation, as mediated by TnC and, in particular, the alternatively spliced FnD domain. PB - Frontiers Media Sa, Lausanne T2 - Frontiers in Immunology T1 - Different Functions of Recombinantly Expressed Domains of Tenascin-C in Glial Scar Formation VL - 11 DO - 10.3389/fimmu.2020.624612 ER -
@article{ author = "Bijelić, Dunja and Adžić, Marija and Perić, Mina and Jakovcevski, Igor and Foerster, Eckart and Schachner, Melitta and Andjus, Pavle R.", year = "2021", abstract = "Extracellular matrix glycoprotein tenascin-C (TnC) is highly expressed in vertebrates during embryonic development and thereafter transiently in tissue niches undergoing extensive remodeling during regeneration after injury. TnC's different functions can be attributed to its multimodular structure represented by distinct domains and alternatively spliced isoforms. Upon central nervous system injury, TnC is upregulated and secreted into the extracellular matrix mainly by astrocytes. The goal of the present study was to elucidate the role of different TnC domains in events that take place after spinal cord injury (SCI). Astrocyte cultures prepared from TnC-deficient (TnC-/-) and wild-type (TnC+/+) mice were scratched and treated with different recombinantly generated TnC fragments. Gap closure, cell proliferation and expression of GFAP and cytokines were determined in these cultures. Gap closure in vitro was found to be delayed by TnC fragments, an effect mainly mediated by decreasing proliferation of astrocytes. The most potent effects were observed with fragments FnD, FnA and their combination. TnC-/- astrocyte cultures exhibited higher GFAP protein and mRNA expression levels, regardless of the type of fragment used for treatment. Application of TnC fragments induced also pro-inflammatory cytokine production by astrocytes in vitro. In vivo, however, the addition of FnD or Fn(D+A) led to a difference between the two genotypes, with higher levels of GFAP expression in TnC+/+ mice. FnD treatment of injured TnC-/- mice increased the density of activated microglia/macrophages in the injury region, while overall cell proliferation in the injury site was not affected. We suggest that altogether these results may explain how the reaction of astrocytes is delayed while their localization is restricted to the border of the injury site to allow microglia/macrophages to form a lesion core during the first stages of glial scar formation, as mediated by TnC and, in particular, the alternatively spliced FnD domain.", publisher = "Frontiers Media Sa, Lausanne", journal = "Frontiers in Immunology", title = "Different Functions of Recombinantly Expressed Domains of Tenascin-C in Glial Scar Formation", volume = "11", doi = "10.3389/fimmu.2020.624612" }
Bijelić, D., Adžić, M., Perić, M., Jakovcevski, I., Foerster, E., Schachner, M.,& Andjus, P. R.. (2021). Different Functions of Recombinantly Expressed Domains of Tenascin-C in Glial Scar Formation. in Frontiers in Immunology Frontiers Media Sa, Lausanne., 11. https://doi.org/10.3389/fimmu.2020.624612
Bijelić D, Adžić M, Perić M, Jakovcevski I, Foerster E, Schachner M, Andjus PR. Different Functions of Recombinantly Expressed Domains of Tenascin-C in Glial Scar Formation. in Frontiers in Immunology. 2021;11. doi:10.3389/fimmu.2020.624612 .
Bijelić, Dunja, Adžić, Marija, Perić, Mina, Jakovcevski, Igor, Foerster, Eckart, Schachner, Melitta, Andjus, Pavle R., "Different Functions of Recombinantly Expressed Domains of Tenascin-C in Glial Scar Formation" in Frontiers in Immunology, 11 (2021), https://doi.org/10.3389/fimmu.2020.624612 . .