Sustained activation of P2X7 induces MMP-2-evoked cleavage and functional purinoceptor inhibition Article Swipe
Chris Young
,
Natalia Chira
,
Justyna Róg
,
Rasha Al-Khalidi
,
Magalie Bénard
,
Ludovic Galas
,
Philippe Chan
,
David Vaudry
,
Krzysztof Zabłocki
,
Dariusz C. Górecki
·
YOU?
·
· 2017
· Open Access
·
· DOI: https://doi.org/10.1093/jmcb/mjx030
YOU?
·
· 2017
· Open Access
·
· DOI: https://doi.org/10.1093/jmcb/mjx030
P2X7 purinoceptor promotes survival or cytotoxicity depending on extracellular adenosine triphosphate (ATP) stimulus intensity controlling its ion channel or P2X7-dependent large pore (LP) functions. Mechanisms governing this operational divergence and functional idiosyncrasy are ill-understood. We have discovered a feedback loop where sustained activation of P2X7 triggers release of active matrix metalloproteinase 2 (MMP-2), which halts ion channel and LP responses via the MMP-2-dependent receptor cleavage. This mechanism operates in cells as diverse as macrophages, dystrophic myoblasts, P2X7-transfected HEK293, and human tumour cells. Given that serum-born MMP-2 activity also blocked receptor functions, P2X7 responses in vivo may decrease in organs with permeable capillaries. Therefore, this mechanism represents an important fine-tuning of P2X7 functions, reliant on both cell-autonomous and extraneous factors. Indeed, it allowed evasion from the ATP-induced cytotoxicity in macrophages and human cancer cells with high P2X7 expression levels. Finally, we demonstrate that P2X7 ablation eliminated gelatinase activity in inflamed dystrophic muscles in vivo. Thus, P2X7 antagonists could be used as an alternative to highly toxic MMP inhibitors in treatments of inflammatory diseases and cancers.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1093/jmcb/mjx030
- OA Status
- gold
- Cited By
- 58
- References
- 51
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2746674724
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W2746674724Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1093/jmcb/mjx030Digital Object Identifier
- Title
-
Sustained activation of P2X7 induces MMP-2-evoked cleavage and functional purinoceptor inhibitionWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2017Year of publication
- Publication date
-
2017-08-11Full publication date if available
- Authors
-
Chris Young, Natalia Chira, Justyna Róg, Rasha Al-Khalidi, Magalie Bénard, Ludovic Galas, Philippe Chan, David Vaudry, Krzysztof Zabłocki, Dariusz C. GóreckiList of authors in order
- Landing page
-
https://doi.org/10.1093/jmcb/mjx030Publisher landing page
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
- OA URL
-
https://hdl.handle.net/2086/14463Direct OA link when available
- Concepts
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Cell biology, In vivo, Matrix metalloproteinase, HEK 293 cells, Cytotoxicity, Transfection, Receptor, Chemistry, Extracellular, In vitro, Biology, Biochemistry, Biotechnology, GeneTop concepts (fields/topics) attached by OpenAlex
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-
58Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 3, 2024: 3, 2023: 23, 2022: 8, 2021: 6Per-year citation counts (last 5 years)
- References (count)
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51Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| primary_location.landing_page_url | https://doi.org/10.1093/jmcb/mjx030 |
| publication_date | 2017-08-11 |
| publication_year | 2017 |
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| corresponding_author_ids | https://openalex.org/A5045428786 |
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| institutions_distinct_count | 10 |
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| sustainable_development_goals[0].display_name | Good health and well-being |
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