Cargando…

MicroRNA-29a Mitigates Laminectomy-Induced Spinal Epidural Fibrosis and Gait Dysregulation by Repressing TGF-β1 and IL-6

Spinal epidural fibrosis is one of the typical features attributable to failed back surgery syndrome, with excessive scar development in the dura and nerve roots. The microRNA-29 family (miR-29s) has been found to act as a fibrogenesis-inhibitory factor that reduces fibrotic matrix overproduction in...

Descripción completa

Detalles Bibliográficos
Autores principales: Lin, I-Ting, Lin, Yu-Han, Lian, Wei-Shiung, Wang, Feng-Sheng, Wu, Re-Wen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10252628/
https://www.ncbi.nlm.nih.gov/pubmed/37298111
http://dx.doi.org/10.3390/ijms24119158
_version_ 1785056216182947840
author Lin, I-Ting
Lin, Yu-Han
Lian, Wei-Shiung
Wang, Feng-Sheng
Wu, Re-Wen
author_facet Lin, I-Ting
Lin, Yu-Han
Lian, Wei-Shiung
Wang, Feng-Sheng
Wu, Re-Wen
author_sort Lin, I-Ting
collection PubMed
description Spinal epidural fibrosis is one of the typical features attributable to failed back surgery syndrome, with excessive scar development in the dura and nerve roots. The microRNA-29 family (miR-29s) has been found to act as a fibrogenesis-inhibitory factor that reduces fibrotic matrix overproduction in various tissues. However, the mechanistic basis of miRNA-29a underlying the overabundant fibrotic matrix synthesis in spinal epidural scars post-laminectomy remained elusive. This study revealed that miR-29a attenuated lumbar laminectomy-induced fibrogenic activity, and epidural fibrotic matrix formation was significantly lessened in the transgenic mice (miR-29aTg) as compared with wild-type mice (WT). Moreover, miR-29aTg limits laminectomy-induced damage and has also been demonstrated to detect walking patterns, footprint distribution, and moving activity. Immunohistochemistry staining of epidural tissue showed that miR-29aTg was a remarkably weak signal of IL-6, TGF-β1, and DNA methyltransferase marker, Dnmt3b, compared to the wild-type mice. Taken together, these results have further strengthened the evidence that miR-29a epigenetic regulation reduces fibrotic matrix formation and spinal epidural fibrotic activity in surgery scars to preserve the integrity of the spinal cord core. This study elucidates and highlights the molecular mechanisms that reduce the incidence of spinal epidural fibrosis, eliminating the risk of gait abnormalities and pain associated with laminectomy.
format Online
Article
Text
id pubmed-10252628
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-102526282023-06-10 MicroRNA-29a Mitigates Laminectomy-Induced Spinal Epidural Fibrosis and Gait Dysregulation by Repressing TGF-β1 and IL-6 Lin, I-Ting Lin, Yu-Han Lian, Wei-Shiung Wang, Feng-Sheng Wu, Re-Wen Int J Mol Sci Article Spinal epidural fibrosis is one of the typical features attributable to failed back surgery syndrome, with excessive scar development in the dura and nerve roots. The microRNA-29 family (miR-29s) has been found to act as a fibrogenesis-inhibitory factor that reduces fibrotic matrix overproduction in various tissues. However, the mechanistic basis of miRNA-29a underlying the overabundant fibrotic matrix synthesis in spinal epidural scars post-laminectomy remained elusive. This study revealed that miR-29a attenuated lumbar laminectomy-induced fibrogenic activity, and epidural fibrotic matrix formation was significantly lessened in the transgenic mice (miR-29aTg) as compared with wild-type mice (WT). Moreover, miR-29aTg limits laminectomy-induced damage and has also been demonstrated to detect walking patterns, footprint distribution, and moving activity. Immunohistochemistry staining of epidural tissue showed that miR-29aTg was a remarkably weak signal of IL-6, TGF-β1, and DNA methyltransferase marker, Dnmt3b, compared to the wild-type mice. Taken together, these results have further strengthened the evidence that miR-29a epigenetic regulation reduces fibrotic matrix formation and spinal epidural fibrotic activity in surgery scars to preserve the integrity of the spinal cord core. This study elucidates and highlights the molecular mechanisms that reduce the incidence of spinal epidural fibrosis, eliminating the risk of gait abnormalities and pain associated with laminectomy. MDPI 2023-05-23 /pmc/articles/PMC10252628/ /pubmed/37298111 http://dx.doi.org/10.3390/ijms24119158 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lin, I-Ting
Lin, Yu-Han
Lian, Wei-Shiung
Wang, Feng-Sheng
Wu, Re-Wen
MicroRNA-29a Mitigates Laminectomy-Induced Spinal Epidural Fibrosis and Gait Dysregulation by Repressing TGF-β1 and IL-6
title MicroRNA-29a Mitigates Laminectomy-Induced Spinal Epidural Fibrosis and Gait Dysregulation by Repressing TGF-β1 and IL-6
title_full MicroRNA-29a Mitigates Laminectomy-Induced Spinal Epidural Fibrosis and Gait Dysregulation by Repressing TGF-β1 and IL-6
title_fullStr MicroRNA-29a Mitigates Laminectomy-Induced Spinal Epidural Fibrosis and Gait Dysregulation by Repressing TGF-β1 and IL-6
title_full_unstemmed MicroRNA-29a Mitigates Laminectomy-Induced Spinal Epidural Fibrosis and Gait Dysregulation by Repressing TGF-β1 and IL-6
title_short MicroRNA-29a Mitigates Laminectomy-Induced Spinal Epidural Fibrosis and Gait Dysregulation by Repressing TGF-β1 and IL-6
title_sort microrna-29a mitigates laminectomy-induced spinal epidural fibrosis and gait dysregulation by repressing tgf-β1 and il-6
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10252628/
https://www.ncbi.nlm.nih.gov/pubmed/37298111
http://dx.doi.org/10.3390/ijms24119158
work_keys_str_mv AT liniting microrna29amitigateslaminectomyinducedspinalepiduralfibrosisandgaitdysregulationbyrepressingtgfb1andil6
AT linyuhan microrna29amitigateslaminectomyinducedspinalepiduralfibrosisandgaitdysregulationbyrepressingtgfb1andil6
AT lianweishiung microrna29amitigateslaminectomyinducedspinalepiduralfibrosisandgaitdysregulationbyrepressingtgfb1andil6
AT wangfengsheng microrna29amitigateslaminectomyinducedspinalepiduralfibrosisandgaitdysregulationbyrepressingtgfb1andil6
AT wurewen microrna29amitigateslaminectomyinducedspinalepiduralfibrosisandgaitdysregulationbyrepressingtgfb1andil6