Tenascin-C fibronectin D domain is involved in the fine-tuning of glial response to CNS injury in vitro
2022
Аутори
Bijelić, DunjaAdžić, Marija
Perić, Mina
Reiss, Gebhard
Milosević, Milena
Andjus, Pavle R.
Jakovcevski, Igor
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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 mi...croglia 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.
Кључне речи:
tenascin-C / scratch wound / microglia / fibronectin III-like domain D / co-culture / astrocytesИзвор:
Frontiers in Cell and Developmental Biology, 2022, 10Издавач:
- Frontiers Media Sa, Lausanne
Финансирање / пројекти:
- Ministry of Education, Science and Technological Development of the Republic of Serbia
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200178 (Универзитет у Београду, Биолошки факултет) (RS-MESTD-inst-2020-200178)
DOI: 10.3389/fcell.2022.952208
ISSN: 2296-634X
WoS: 000852528100001
Scopus: 2-s2.0-85138110466
Институција/група
Institut za molekularnu genetiku i genetičko inženjerstvoTY - 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 . .