The NFATc1/P2X7 receptor relationship in human intervertebral disc cells
A comprehensive understanding of the molecules that play key roles in the physiological and pathological homeostasis of the human intervertebral disc (IVD) remains challenging, as does the development of new therapeutic treatments. We recently found a positive correlation between IVD degeneration (I...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2024.1368318/full |
| _version_ | 1827294194803146752 |
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| author | Maria Pina Notarangelo Letizia Penolazzi Elisabetta Lambertini Simonetta Falzoni Pasquale De Bonis Cristina Capanni Cristina Capanni Francesco Di Virgilio Roberta Piva |
| author_facet | Maria Pina Notarangelo Letizia Penolazzi Elisabetta Lambertini Simonetta Falzoni Pasquale De Bonis Cristina Capanni Cristina Capanni Francesco Di Virgilio Roberta Piva |
| author_sort | Maria Pina Notarangelo |
| collection | DOAJ |
| description | A comprehensive understanding of the molecules that play key roles in the physiological and pathological homeostasis of the human intervertebral disc (IVD) remains challenging, as does the development of new therapeutic treatments. We recently found a positive correlation between IVD degeneration (IDD) and P2X7 receptor (P2X7R) expression increases both in the cytoplasm and in the nucleus. Using immunocytochemistry, reverse transcription PCR (RT-PCR), overexpression, and chromatin immunoprecipitation, we found that NFATc1 and hypoxia-inducible factor-1α (HIF-1α) are critical regulators of P2X7R. Both transcription factors are recruited at the promoter of the P2RX7 gene and involved in its positive and negative regulation, respectively. Furthermore, using the proximity ligation assay, we revealed that P2X7R and NFATc1 form a molecular complex and that P2X7R is closely associated with lamin A/C, a major component of the nuclear lamina. Collectively, our study identifies, for the first time, P2X7R and NFATc1 as markers of IVD degeneration and demonstrates that both NFATc1 and lamin A/C are interaction partners of P2X7R. |
| first_indexed | 2024-04-24T13:52:39Z |
| format | Article |
| id | doaj.art-9535fd74f6e64ed9908505704d26553a |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-24T13:52:39Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-9535fd74f6e64ed9908505704d26553a2024-04-04T04:24:44ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2024-04-011210.3389/fcell.2024.13683181368318The NFATc1/P2X7 receptor relationship in human intervertebral disc cellsMaria Pina Notarangelo0Letizia Penolazzi1Elisabetta Lambertini2Simonetta Falzoni3Pasquale De Bonis4Cristina Capanni5Cristina Capanni6Francesco Di Virgilio7Roberta Piva8Department of Neuroscience and Rehabilitation, University of Ferrara, Ferrara, ItalyDepartment of Neuroscience and Rehabilitation, University of Ferrara, Ferrara, ItalyDepartment of Chemical, Pharmaceutical and Agricultural Sciences of the University of Ferrara, Ferrara, ItalyDepartment of Medical Sciences, University of Ferrara, Ferrara, ItalyNeurosurgery Department, Sant’Anna University Hospital, Ferrara, ItalyCNR Institute of Molecular Genetics “Luigi Luca Cavalli-Sforza”, Unit of Bologna, Bologna, ItalyIRCCS Rizzoli Orthopedic Institute, Bologna, ItalyDepartment of Medical Sciences, University of Ferrara, Ferrara, ItalyDepartment of Neuroscience and Rehabilitation, University of Ferrara, Ferrara, ItalyA comprehensive understanding of the molecules that play key roles in the physiological and pathological homeostasis of the human intervertebral disc (IVD) remains challenging, as does the development of new therapeutic treatments. We recently found a positive correlation between IVD degeneration (IDD) and P2X7 receptor (P2X7R) expression increases both in the cytoplasm and in the nucleus. Using immunocytochemistry, reverse transcription PCR (RT-PCR), overexpression, and chromatin immunoprecipitation, we found that NFATc1 and hypoxia-inducible factor-1α (HIF-1α) are critical regulators of P2X7R. Both transcription factors are recruited at the promoter of the P2RX7 gene and involved in its positive and negative regulation, respectively. Furthermore, using the proximity ligation assay, we revealed that P2X7R and NFATc1 form a molecular complex and that P2X7R is closely associated with lamin A/C, a major component of the nuclear lamina. Collectively, our study identifies, for the first time, P2X7R and NFATc1 as markers of IVD degeneration and demonstrates that both NFATc1 and lamin A/C are interaction partners of P2X7R.https://www.frontiersin.org/articles/10.3389/fcell.2024.1368318/fullintervertebral disc cellsP2X7 purinergic receptorNFATc1 transcription factorhypoxia-inducible factor-1αproximity ligation assaylamin A/C |
| spellingShingle | Maria Pina Notarangelo Letizia Penolazzi Elisabetta Lambertini Simonetta Falzoni Pasquale De Bonis Cristina Capanni Cristina Capanni Francesco Di Virgilio Roberta Piva The NFATc1/P2X7 receptor relationship in human intervertebral disc cells Frontiers in Cell and Developmental Biology intervertebral disc cells P2X7 purinergic receptor NFATc1 transcription factor hypoxia-inducible factor-1α proximity ligation assay lamin A/C |
| title | The NFATc1/P2X7 receptor relationship in human intervertebral disc cells |
| title_full | The NFATc1/P2X7 receptor relationship in human intervertebral disc cells |
| title_fullStr | The NFATc1/P2X7 receptor relationship in human intervertebral disc cells |
| title_full_unstemmed | The NFATc1/P2X7 receptor relationship in human intervertebral disc cells |
| title_short | The NFATc1/P2X7 receptor relationship in human intervertebral disc cells |
| title_sort | nfatc1 p2x7 receptor relationship in human intervertebral disc cells |
| topic | intervertebral disc cells P2X7 purinergic receptor NFATc1 transcription factor hypoxia-inducible factor-1α proximity ligation assay lamin A/C |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2024.1368318/full |
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