TY  - JOUR
AU  - Bijelić, Dunja
AU  - Adžić, Marija
AU  - Perić, Mina
AU  - Reiss, Gebhard
AU  - Milosević, Milena
AU  - Andjus, Pavle R.
AU  - Jakovcevski, Igor
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1522
AB  - Understanding processes that occur after injuries to the central nervous system is essential in order to gain insight into how the restoration of function can be improved. Extracellular glycoprotein tenascin-C (TnC) has numerous functions in wound healing process depending on the expression time, location, isoform and binding partners which makes it interesting to study in this context. We used an in vitro injury model, the mixed culture of cortical astrocytes and microglia, and observed that without TnC microglial cells tend to populate gap area in greater numbers and proliferate more, whereas astrocytes build up in the border region to promote faster gap closure. Alternatively spliced domain of TnC, fibronectin type III-like repeat D (FnD) strongly affected physiological properties and morphology of both astrocytes and microglia in this injury model. The rate of microglial proliferation in the injury region decreased significantly with the addition of FnD. Additionally, density of microglia also decreased, in part due to reduced proliferation, and possibly due to reduced migration and increased contact inhibition between enlarged FnD-treated cells. Overall morphology of FnD-treated microglia resembled the activated pro-inflammatory cells, and elevated expression of iNOS was in accordance with this phenotype. The effect of FnD on astrocytes was different, as it did not affect their proliferation, but stimulated migration of reactivated astrocytes into the scratched area 48 h after the lesion. Elevated expression and secretion of TNF-alpha and IL-1 beta upon FnD treatment indicated the onset of inflammation. Furthermore, on Western blots we observed increased intensity of precursor bands of beta 1 integrin and appearance of monomeric bands of P2Y12R after FnD treatment which substantiates and clarifies its role in cellular shape and motility changes. Our results show versatile functions of TnC and in particular FnD after injury, mostly contributing to ongoing inflammation in the injury region. Based on our findings, FnD might be instrumental in limiting immune cell infiltration, and promoting astrocyte migration within the injury region, thus influencing spaciotemporal organization of the wound and surrounding area.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Cell and Developmental Biology
T1  - Tenascin-C fibronectin D domain is involved in the fine-tuning of glial response to CNS injury in vitro
VL  - 10
DO  - 10.3389/fcell.2022.952208
ER  - 

@article{
author = "Bijelić, Dunja and Adžić, Marija and Perić, Mina and Reiss, Gebhard and Milosević, Milena and Andjus, Pavle R. and Jakovcevski, Igor",
year = "2022",
abstract = "Understanding processes that occur after injuries to the central nervous system is essential in order to gain insight into how the restoration of function can be improved. Extracellular glycoprotein tenascin-C (TnC) has numerous functions in wound healing process depending on the expression time, location, isoform and binding partners which makes it interesting to study in this context. We used an in vitro injury model, the mixed culture of cortical astrocytes and microglia, and observed that without TnC microglial cells tend to populate gap area in greater numbers and proliferate more, whereas astrocytes build up in the border region to promote faster gap closure. Alternatively spliced domain of TnC, fibronectin type III-like repeat D (FnD) strongly affected physiological properties and morphology of both astrocytes and microglia in this injury model. The rate of microglial proliferation in the injury region decreased significantly with the addition of FnD. Additionally, density of microglia also decreased, in part due to reduced proliferation, and possibly due to reduced migration and increased contact inhibition between enlarged FnD-treated cells. Overall morphology of FnD-treated microglia resembled the activated pro-inflammatory cells, and elevated expression of iNOS was in accordance with this phenotype. The effect of FnD on astrocytes was different, as it did not affect their proliferation, but stimulated migration of reactivated astrocytes into the scratched area 48 h after the lesion. Elevated expression and secretion of TNF-alpha and IL-1 beta upon FnD treatment indicated the onset of inflammation. Furthermore, on Western blots we observed increased intensity of precursor bands of beta 1 integrin and appearance of monomeric bands of P2Y12R after FnD treatment which substantiates and clarifies its role in cellular shape and motility changes. Our results show versatile functions of TnC and in particular FnD after injury, mostly contributing to ongoing inflammation in the injury region. Based on our findings, FnD might be instrumental in limiting immune cell infiltration, and promoting astrocyte migration within the injury region, thus influencing spaciotemporal organization of the wound and surrounding area.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Cell and Developmental Biology",
title = "Tenascin-C fibronectin D domain is involved in the fine-tuning of glial response to CNS injury in vitro",
volume = "10",
doi = "10.3389/fcell.2022.952208"
}

Bijelić, D., Adžić, M., Perić, M., Reiss, G., Milosević, M., Andjus, P. R.,& Jakovcevski, I.. (2022). Tenascin-C fibronectin D domain is involved in the fine-tuning of glial response to CNS injury in vitro. in Frontiers in Cell and Developmental Biology
Frontiers Media Sa, Lausanne., 10.
https://doi.org/10.3389/fcell.2022.952208

Bijelić D, Adžić M, Perić M, Reiss G, Milosević M, Andjus PR, Jakovcevski I. Tenascin-C fibronectin D domain is involved in the fine-tuning of glial response to CNS injury in vitro. in Frontiers in Cell and Developmental Biology. 2022;10.
doi:10.3389/fcell.2022.952208 .

Bijelić, Dunja, Adžić, Marija, Perić, Mina, Reiss, Gebhard, Milosević, Milena, Andjus, Pavle R., Jakovcevski, Igor, "Tenascin-C fibronectin D domain is involved in the fine-tuning of glial response to CNS injury in vitro" in Frontiers in Cell and Developmental Biology, 10 (2022),
https://doi.org/10.3389/fcell.2022.952208 . .

TY  - 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/123456789/1423
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Immunology
T1  - Different Functions of Recombinantly Expressed Domains of Tenascin-C in Glial Scar Formation (vol 11, 3944, 2021)
VL  - 12
DO  - 10.3389/fimmu.2021.672476
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",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Immunology",
title = "Different Functions of Recombinantly Expressed Domains of Tenascin-C in Glial Scar Formation (vol 11, 3944, 2021)",
volume = "12",
doi = "10.3389/fimmu.2021.672476"
}

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 (vol 11, 3944, 2021). in Frontiers in Immunology
Frontiers Media Sa, Lausanne., 12.
https://doi.org/10.3389/fimmu.2021.672476

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 (vol 11, 3944, 2021). in Frontiers in Immunology. 2021;12.
doi:10.3389/fimmu.2021.672476 .

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 (vol 11, 3944, 2021)" in Frontiers in Immunology, 12 (2021),
https://doi.org/10.3389/fimmu.2021.672476 . .

TY  - 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 . .