| Title: |
Factor XII protects neurons from apoptosis by epidermal and hepatocyte growth factor receptor-dependent mechanisms |
| Authors: |
Garnier E.; Levard D.; Ali C.; Buendia I.; Hommet Y.; Gauberti M.; Crepaldi T.; Comoglio P.; Rubio M.; Vivien D.; Docagne F.; Martinez de Lizarrondo S. |
| Contributors: |
Garnier E.; Levard D.; Ali C.; Buendia I.; Hommet Y.; Gauberti M.; Crepaldi T.; Comoglio P.; Rubio M.; Vivien D.; Docagne F.; Martinez de Lizarrondo S. |
| Publication Year: |
2021 |
| Collection: |
Università degli studi di Torino: AperTo (Archivio Istituzionale ad Accesso Aperto) |
| Subject Terms: |
apoptosi; contact pathway; intrinsic pathway; neuroprotection; thromboinflammation |
| Description: |
Background: Factor XII (FXII) is a serine protease that participates in the intrinsic coagulation pathway. Several studies have shown that plasma FXII exerts a deleterious role in cerebral ischemia and traumatic brain injury by promoting thrombo-inflammation. Nevertheless, the impact of FXII on neuronal cell fate remains unknown. Objectives: We investigated the role of FXII and FXIIa in neuronal injury and apoptotic cell death. Methods: We tested the neuroprotective roles of FXII and FXIIa in an experimental model of neuronal injury induced by stereotaxic intracerebral injection of N-methyl-D-aspartic acid (NMDA) in vivo and in a model of apoptotic death of murine primary neuronal cultures through serum deprivation in vitro. Results: Here, we found that exogenous FXII and FXIIa reduce brain lesions induced by NMDA injection in vivo. Furthermore, FXII protects cultured neurons from apoptosis through a growth factor--like effect. This mechanism was triggered by direct interaction with epidermal growth factor (EGF) receptor and subsequent activation of this receptor. Interestingly, the “proteolytically” active and two-chain form of FXII, FXIIa, exerts its protective effects by an alternative signaling pathway. FXIIa activates the pro-form of hepatocyte growth factor (HGF) into HGF, which in turn activated the HGF receptor (HGFR) pathway. Conclusion: This study describes two novel mechanisms of action of FXII and identifies neurons as target cells for the protective effects of single and two-chain forms of FXII. Therefore, inhibition of FXII in neurological disorders may have deleterious effects by preventing its beneficial effects on neuronal survival. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/34060720; info:eu-repo/semantics/altIdentifier/wos/WOS:000667704300001; firstpage:1; lastpage:7; numberofpages:7; journal:JOURNAL OF THROMBOSIS AND HAEMOSTASIS; http://hdl.handle.net/2318/1794801; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85108809880 |
| DOI: |
10.1111/jth.15414 |
| Availability: |
http://hdl.handle.net/2318/1794801; https://doi.org/10.1111/jth.15414 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.6EC5D822 |
| Database: |
BASE |