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Adipose-derived stromal cells improve functional recovery after spinal cord injury through TGF-β1/Smad3/PLOD2 pathway activation
Transplantation of mesenchymal stromal cells (MSCs) improves functional recovery in experimental models of spinal cord injury (SCI), but the mechanism is not fully understood. Activation of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a collagen-modifying enzyme, reportedly follows MS...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906172/ https://www.ncbi.nlm.nih.gov/pubmed/33495412 http://dx.doi.org/10.18632/aging.202399 |
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author | Li, Fang Liu, Hua Zhang, Kun Xiao, Dong-Jie Wang, Chang Wang, Yun-Shan |
author_facet | Li, Fang Liu, Hua Zhang, Kun Xiao, Dong-Jie Wang, Chang Wang, Yun-Shan |
author_sort | Li, Fang |
collection | PubMed |
description | Transplantation of mesenchymal stromal cells (MSCs) improves functional recovery in experimental models of spinal cord injury (SCI), but the mechanism is not fully understood. Activation of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a collagen-modifying enzyme, reportedly follows MSC transplantation in an SCI animal model. We investigated the regulation of PLOD2 expression and its potential contribution to the neuroprotective effects of adipose-derived stromal cells (ADSCs) following mechanical injury to neurons in vitro and SCI in vivo. ADSCs enhanced wound healing in vitro and promoted functional recovery after their implantation near injury sites in a rat SCI model. These effects correlated with upregulation of PLOD2, MAP2, NSE and GAP43, and downregulation of GFAP, which is indicative of improved neuronal survival and axonal regeneration as well as reduced glial scar formation. The neurorestorative effect of ADSCs was weakened after inhibition of PLOD2 expression. ADSCs appeared to induce PLOD2 upregulation via TGF-β1 secretion, as ADSC-mediated PLOD2 expression, neuronal survival, and functional recovery after SCI were largely prevented by SB431542, a TGF-(1 receptor inhibitor. These findings indicate that ADSCs reduce lesion size and promote functional recovery after SCI mainly through activation of a TGF-β1/P-Samd3/PLOD2 pathway in spinal cord neurons. |
format | Online Article Text |
id | pubmed-7906172 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
spelling | pubmed-79061722021-03-04 Adipose-derived stromal cells improve functional recovery after spinal cord injury through TGF-β1/Smad3/PLOD2 pathway activation Li, Fang Liu, Hua Zhang, Kun Xiao, Dong-Jie Wang, Chang Wang, Yun-Shan Aging (Albany NY) Research Paper Transplantation of mesenchymal stromal cells (MSCs) improves functional recovery in experimental models of spinal cord injury (SCI), but the mechanism is not fully understood. Activation of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a collagen-modifying enzyme, reportedly follows MSC transplantation in an SCI animal model. We investigated the regulation of PLOD2 expression and its potential contribution to the neuroprotective effects of adipose-derived stromal cells (ADSCs) following mechanical injury to neurons in vitro and SCI in vivo. ADSCs enhanced wound healing in vitro and promoted functional recovery after their implantation near injury sites in a rat SCI model. These effects correlated with upregulation of PLOD2, MAP2, NSE and GAP43, and downregulation of GFAP, which is indicative of improved neuronal survival and axonal regeneration as well as reduced glial scar formation. The neurorestorative effect of ADSCs was weakened after inhibition of PLOD2 expression. ADSCs appeared to induce PLOD2 upregulation via TGF-β1 secretion, as ADSC-mediated PLOD2 expression, neuronal survival, and functional recovery after SCI were largely prevented by SB431542, a TGF-(1 receptor inhibitor. These findings indicate that ADSCs reduce lesion size and promote functional recovery after SCI mainly through activation of a TGF-β1/P-Samd3/PLOD2 pathway in spinal cord neurons. Impact Journals 2021-01-20 /pmc/articles/PMC7906172/ /pubmed/33495412 http://dx.doi.org/10.18632/aging.202399 Text en Copyright: © 2021 Li et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Li, Fang Liu, Hua Zhang, Kun Xiao, Dong-Jie Wang, Chang Wang, Yun-Shan Adipose-derived stromal cells improve functional recovery after spinal cord injury through TGF-β1/Smad3/PLOD2 pathway activation |
title | Adipose-derived stromal cells improve functional recovery after spinal cord injury through TGF-β1/Smad3/PLOD2 pathway activation |
title_full | Adipose-derived stromal cells improve functional recovery after spinal cord injury through TGF-β1/Smad3/PLOD2 pathway activation |
title_fullStr | Adipose-derived stromal cells improve functional recovery after spinal cord injury through TGF-β1/Smad3/PLOD2 pathway activation |
title_full_unstemmed | Adipose-derived stromal cells improve functional recovery after spinal cord injury through TGF-β1/Smad3/PLOD2 pathway activation |
title_short | Adipose-derived stromal cells improve functional recovery after spinal cord injury through TGF-β1/Smad3/PLOD2 pathway activation |
title_sort | adipose-derived stromal cells improve functional recovery after spinal cord injury through tgf-β1/smad3/plod2 pathway activation |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906172/ https://www.ncbi.nlm.nih.gov/pubmed/33495412 http://dx.doi.org/10.18632/aging.202399 |
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