Cargando…

Inhibition of TERC inhibits neural apoptosis and inflammation in spinal cord injury through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis

This study investigated the function of telomerase RNA component (TERC) in spinal cord injury (SCI). SCI models were established in rats via laminectomy and PC-12 cells were treated with lipopolysaccharide (LPS). TERC and miR-34a-5p expressions in cells and rat spinal cords were detected by quantita...

Descripción completa

Detalles Bibliográficos
Autores principales: Ding, Weiguo, Xu, Weixing, Lu, Di, Sheng, Hongfeng, Xu, Xinwei, Xu, Bin, Zheng, Aote
Formato: Online Artículo Texto
Lenguaje:English
Publicado: De Gruyter 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9883688/
https://www.ncbi.nlm.nih.gov/pubmed/36742154
http://dx.doi.org/10.1515/med-2022-0619
_version_ 1784879558796771328
author Ding, Weiguo
Xu, Weixing
Lu, Di
Sheng, Hongfeng
Xu, Xinwei
Xu, Bin
Zheng, Aote
author_facet Ding, Weiguo
Xu, Weixing
Lu, Di
Sheng, Hongfeng
Xu, Xinwei
Xu, Bin
Zheng, Aote
author_sort Ding, Weiguo
collection PubMed
description This study investigated the function of telomerase RNA component (TERC) in spinal cord injury (SCI). SCI models were established in rats via laminectomy and PC-12 cells were treated with lipopolysaccharide (LPS). TERC and miR-34a-5p expressions in cells and rat spinal cords were detected by quantitative reverse transcription polymerase chain reaction, followed by overexpression/knockdown of TERC/miR-34a-5p. Spinal cord histopathological changes were examined via hematoxylin–eosin staining. miR-34a-5p′ relation with TERC and XBP-1 was predicted by TargetScan and checked by dual-luciferase reporter/RNA immunoprecipitation assays. Cell biological behaviors were assessed by Cell counting kit-8, wound healing, Transwell, and flow cytometry assays. XBP-1 and inflammation/apoptosis-related protein expressions were analyzed by western blot. TERC was upregulated and miR-34a-5p was low-expressed in SCI tissues and LPS-induced PC-12 cells. TERC-knockdown alleviated histopathological abnormalities yet upregulated miR-34a-5p in SCI tissues. In LPS-induced PC-12 cells, TERC knockdown promoted cell viability, migration, invasion, and inhibited apoptosis, while TERC overexpression ran oppositely. TERC knockdown downregulated the XBP-1, IL-6, TNF-α, Bax, p-p38/t-p38, and cleaved caspase-9/-3, but upregulated Bcl-2 and p-Akt/t-Akt. TERC targeted miR-34a-5p, which further targeted XBP-1. miR-34a-5p downregulation exerted effects opposite to and offset TERC knockdown-induced effects. TERC knockdown facilitated the regeneration of neuron tissues yet inhibited inflammation in SCI through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis.
format Online
Article
Text
id pubmed-9883688
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher De Gruyter
record_format MEDLINE/PubMed
spelling pubmed-98836882023-02-03 Inhibition of TERC inhibits neural apoptosis and inflammation in spinal cord injury through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis Ding, Weiguo Xu, Weixing Lu, Di Sheng, Hongfeng Xu, Xinwei Xu, Bin Zheng, Aote Open Med (Wars) Research Article This study investigated the function of telomerase RNA component (TERC) in spinal cord injury (SCI). SCI models were established in rats via laminectomy and PC-12 cells were treated with lipopolysaccharide (LPS). TERC and miR-34a-5p expressions in cells and rat spinal cords were detected by quantitative reverse transcription polymerase chain reaction, followed by overexpression/knockdown of TERC/miR-34a-5p. Spinal cord histopathological changes were examined via hematoxylin–eosin staining. miR-34a-5p′ relation with TERC and XBP-1 was predicted by TargetScan and checked by dual-luciferase reporter/RNA immunoprecipitation assays. Cell biological behaviors were assessed by Cell counting kit-8, wound healing, Transwell, and flow cytometry assays. XBP-1 and inflammation/apoptosis-related protein expressions were analyzed by western blot. TERC was upregulated and miR-34a-5p was low-expressed in SCI tissues and LPS-induced PC-12 cells. TERC-knockdown alleviated histopathological abnormalities yet upregulated miR-34a-5p in SCI tissues. In LPS-induced PC-12 cells, TERC knockdown promoted cell viability, migration, invasion, and inhibited apoptosis, while TERC overexpression ran oppositely. TERC knockdown downregulated the XBP-1, IL-6, TNF-α, Bax, p-p38/t-p38, and cleaved caspase-9/-3, but upregulated Bcl-2 and p-Akt/t-Akt. TERC targeted miR-34a-5p, which further targeted XBP-1. miR-34a-5p downregulation exerted effects opposite to and offset TERC knockdown-induced effects. TERC knockdown facilitated the regeneration of neuron tissues yet inhibited inflammation in SCI through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis. De Gruyter 2023-01-24 /pmc/articles/PMC9883688/ /pubmed/36742154 http://dx.doi.org/10.1515/med-2022-0619 Text en © 2023 the author(s), published by De Gruyter https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License.
spellingShingle Research Article
Ding, Weiguo
Xu, Weixing
Lu, Di
Sheng, Hongfeng
Xu, Xinwei
Xu, Bin
Zheng, Aote
Inhibition of TERC inhibits neural apoptosis and inflammation in spinal cord injury through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis
title Inhibition of TERC inhibits neural apoptosis and inflammation in spinal cord injury through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis
title_full Inhibition of TERC inhibits neural apoptosis and inflammation in spinal cord injury through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis
title_fullStr Inhibition of TERC inhibits neural apoptosis and inflammation in spinal cord injury through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis
title_full_unstemmed Inhibition of TERC inhibits neural apoptosis and inflammation in spinal cord injury through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis
title_short Inhibition of TERC inhibits neural apoptosis and inflammation in spinal cord injury through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis
title_sort inhibition of terc inhibits neural apoptosis and inflammation in spinal cord injury through akt activation and p-38 inhibition via the mir-34a-5p/xbp-1 axis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9883688/
https://www.ncbi.nlm.nih.gov/pubmed/36742154
http://dx.doi.org/10.1515/med-2022-0619
work_keys_str_mv AT dingweiguo inhibitionoftercinhibitsneuralapoptosisandinflammationinspinalcordinjurythroughaktactivationandp38inhibitionviathemir34a5pxbp1axis
AT xuweixing inhibitionoftercinhibitsneuralapoptosisandinflammationinspinalcordinjurythroughaktactivationandp38inhibitionviathemir34a5pxbp1axis
AT ludi inhibitionoftercinhibitsneuralapoptosisandinflammationinspinalcordinjurythroughaktactivationandp38inhibitionviathemir34a5pxbp1axis
AT shenghongfeng inhibitionoftercinhibitsneuralapoptosisandinflammationinspinalcordinjurythroughaktactivationandp38inhibitionviathemir34a5pxbp1axis
AT xuxinwei inhibitionoftercinhibitsneuralapoptosisandinflammationinspinalcordinjurythroughaktactivationandp38inhibitionviathemir34a5pxbp1axis
AT xubin inhibitionoftercinhibitsneuralapoptosisandinflammationinspinalcordinjurythroughaktactivationandp38inhibitionviathemir34a5pxbp1axis
AT zhengaote inhibitionoftercinhibitsneuralapoptosisandinflammationinspinalcordinjurythroughaktactivationandp38inhibitionviathemir34a5pxbp1axis