Urokinase receptor regulates nerve regeneration through its interaction with α5β1-integrin - 14/03/20
, M.N. Karagyaur c, K.D. Rysenkova a, b, V.Yu. Sysoeva b, N.A. Mironov b, G.D. Sagaradze c, A.A. Az'muko d, V.S. Popov b, K.A. Rubina b, e, V.A. Tkachuk a, b, cBienvenue sur EM-consulte, la référence des professionnels de santé.
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| pages | 17 |
| Iconographies | 15 |
| Vidéos | 0 |
| Autres | 0 |
Highlights |
• | uPAR deficiency affects nerve fiber recovery, axonal re-growth and re-myelination. |
• | uPAR expression increases in the absence of uPA. |
• | uPAR colocalizes with α5β1 integrin in uPA-deficient mice. |
• | uPAR is an important regulator of α5β1 integrin expression and function. |
• | uPAR-α5β1-integrin interaction is significant for neuritogenesis. |
Abstract |
Purpose |
Urokinase receptor (uPAR) promotes extracellular matrix proteolysis, regulates adhesion and cell migration, transduces intracellular signals through interactions with the lateral partners. The expression of uPAR and urokinase (uPA) is significantly upregulated in peripheral nerves after injury, however, little is known about uPAR function in nerve regeneration or the molecular mechanisms involved. The purpose of this study is to investigate the role of uPAR in nerve regeneration after traumatic injury of n. Peroneus communis in uPA-/-, uPAR-/- or control mice (WT) and in neuritogenesis in an in vitro Neuro 2A cell model.
Results |
Electrophysiological analysis indicates that nerve recovery is significantly impaired in uPAR-/- mice, but not in uPA-/- mice. These data correlate with the reduced amount of NF200-positive axons in regenerating nerves from uPAR-/- mice compared to uPA-/- or control mice. There is an increase in uPAR expression and remarkable colocalization of uPAR with α5 and β1 integrin in uPA-/- mice in recovering nerves, pointing to a potential link between uPAR and its lateral partner α5β1-integrin. Using an in vitro model of neuritogenesis and α325 blocking peptide, which abrogates uPAR-α5β1 interaction in Neuro 2A cells but has no effect on their function, we have further confirmed the significance of uPAR-α5β1 interaction.
Conclusion |
Taken together, we report evidence pointing to an important role of uPAR, rather than uPA, in peripheral nerve recovery and neuritogenesis.
Le texte complet de cet article est disponible en PDF.Abbreviations : BDNF, CNAP, CNS, ECM, EGFR, GPI, IGF-1R, PAs, PDGFR, PNS, uPA, uPAR
Keywords : Peripheral nerve regeneration, Urokinase, uPAR, Integrin, Neuritogenesis
Plan
Vol 125
Article 110008- mai 2020 Retour au numéro
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