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Silencing SUMO2 promotes protection against degradation and apoptosis of nucleus pulposus cells through p53 signaling pathway in intervertebral disc degeneration

Objective: Intervertebral disc degeneration (IDD), as a common cause of back pain, is related to the promotion of cellular senescence and reduction in proliferation. Based on recent studies, small ubiquitin-related modifier (SUMO) proteins have been implicated in various biological functions. Theref...

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Autores principales: Jin, Liu-Zhong, Lu, Ji-Shou, Gao, Jian-Wen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023941/
https://www.ncbi.nlm.nih.gov/pubmed/29700214
http://dx.doi.org/10.1042/BSR20171523
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author Jin, Liu-Zhong
Lu, Ji-Shou
Gao, Jian-Wen
author_facet Jin, Liu-Zhong
Lu, Ji-Shou
Gao, Jian-Wen
author_sort Jin, Liu-Zhong
collection PubMed
description Objective: Intervertebral disc degeneration (IDD), as a common cause of back pain, is related to the promotion of cellular senescence and reduction in proliferation. Based on recent studies, small ubiquitin-related modifier (SUMO) proteins have been implicated in various biological functions. Therefore, in the present study, we investigated the effects of SUMO2 on proliferation and senescence of nucleus pulposus cells (NPCs) via mediation of p53 signaling pathway in rat models of IDD. Methods: After the establishment of rat models of IDD for the measurement of positive expression of SUMO2/3 protein, the mRNA and protein levels of SUMO2, molecular phenotype [matrix metalloproteinase-2 (MMP-2) and hypoxia-inducible factor-1α (HIF-1α)] and p53 signaling pathway-related genes [p21, murine double minute-2 (MDM2), growth arrest and DNA-damage-inducible protein 45 α (GADD45α), cyclin-dependent kinase 2/4 (CDK2/4), and CyclinB1] were determined, followed by the detection of cell proliferation, cell cycle, apoptosis, and cell senescence. Results: The rat models of IDD were successfully constructed. The results obtained showed that there was a higher positive expression of SUMO2/3 protein in IDD rats. Moreover, the silencing of the SUMO2 gene decreases the levels of SUMO2, p53, p21, MDM2, GADD45α, MMP-2, and HIF-1α expressions and p53 phosphorylation level while it increases the levels of CDK2/4 and CyclinB1 expressions. In addition, SUMO2 gene silencing enhances proliferation and suppresses apoptosis and cell senescence of NPCs. Conclusion: In conclusion, SUMO2 gene silencing promotes proliferation, and inhibits the apoptosis and senescence of NPCs in rats with IDD through the down-regulation of the p53 signaling pathway. Thus, SUMO2 is a potential target in the treatment of IDD.
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spelling pubmed-60239412018-07-06 Silencing SUMO2 promotes protection against degradation and apoptosis of nucleus pulposus cells through p53 signaling pathway in intervertebral disc degeneration Jin, Liu-Zhong Lu, Ji-Shou Gao, Jian-Wen Biosci Rep Research Articles Objective: Intervertebral disc degeneration (IDD), as a common cause of back pain, is related to the promotion of cellular senescence and reduction in proliferation. Based on recent studies, small ubiquitin-related modifier (SUMO) proteins have been implicated in various biological functions. Therefore, in the present study, we investigated the effects of SUMO2 on proliferation and senescence of nucleus pulposus cells (NPCs) via mediation of p53 signaling pathway in rat models of IDD. Methods: After the establishment of rat models of IDD for the measurement of positive expression of SUMO2/3 protein, the mRNA and protein levels of SUMO2, molecular phenotype [matrix metalloproteinase-2 (MMP-2) and hypoxia-inducible factor-1α (HIF-1α)] and p53 signaling pathway-related genes [p21, murine double minute-2 (MDM2), growth arrest and DNA-damage-inducible protein 45 α (GADD45α), cyclin-dependent kinase 2/4 (CDK2/4), and CyclinB1] were determined, followed by the detection of cell proliferation, cell cycle, apoptosis, and cell senescence. Results: The rat models of IDD were successfully constructed. The results obtained showed that there was a higher positive expression of SUMO2/3 protein in IDD rats. Moreover, the silencing of the SUMO2 gene decreases the levels of SUMO2, p53, p21, MDM2, GADD45α, MMP-2, and HIF-1α expressions and p53 phosphorylation level while it increases the levels of CDK2/4 and CyclinB1 expressions. In addition, SUMO2 gene silencing enhances proliferation and suppresses apoptosis and cell senescence of NPCs. Conclusion: In conclusion, SUMO2 gene silencing promotes proliferation, and inhibits the apoptosis and senescence of NPCs in rats with IDD through the down-regulation of the p53 signaling pathway. Thus, SUMO2 is a potential target in the treatment of IDD. Portland Press Ltd. 2018-06-29 /pmc/articles/PMC6023941/ /pubmed/29700214 http://dx.doi.org/10.1042/BSR20171523 Text en © 2018 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Articles
Jin, Liu-Zhong
Lu, Ji-Shou
Gao, Jian-Wen
Silencing SUMO2 promotes protection against degradation and apoptosis of nucleus pulposus cells through p53 signaling pathway in intervertebral disc degeneration
title Silencing SUMO2 promotes protection against degradation and apoptosis of nucleus pulposus cells through p53 signaling pathway in intervertebral disc degeneration
title_full Silencing SUMO2 promotes protection against degradation and apoptosis of nucleus pulposus cells through p53 signaling pathway in intervertebral disc degeneration
title_fullStr Silencing SUMO2 promotes protection against degradation and apoptosis of nucleus pulposus cells through p53 signaling pathway in intervertebral disc degeneration
title_full_unstemmed Silencing SUMO2 promotes protection against degradation and apoptosis of nucleus pulposus cells through p53 signaling pathway in intervertebral disc degeneration
title_short Silencing SUMO2 promotes protection against degradation and apoptosis of nucleus pulposus cells through p53 signaling pathway in intervertebral disc degeneration
title_sort silencing sumo2 promotes protection against degradation and apoptosis of nucleus pulposus cells through p53 signaling pathway in intervertebral disc degeneration
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023941/
https://www.ncbi.nlm.nih.gov/pubmed/29700214
http://dx.doi.org/10.1042/BSR20171523
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