| First Author | Klimovich PS | Year | 2020 |
| Journal | Biomed Pharmacother | Volume | 125 |
| Pages | 110008 | PubMed ID | 32187956 |
| Mgi Jnum | J:299803 | Mgi Id | MGI:6490688 |
| Doi | 10.1016/j.biopha.2020.110008 | Citation | Klimovich PS, et al. (2020) Urokinase receptor regulates nerve regeneration through its interaction with alpha5beta1-integrin. Biomed Pharmacother 125:110008 |
| abstractText | 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 alpha5 and beta1 integrin in uPA-/- mice in recovering nerves, pointing to a potential link between uPAR and its lateral partner alpha5beta1-integrin. Using an in vitro model of neuritogenesis and alpha325 blocking peptide, which abrogates uPAR-alpha5beta1 interaction in Neuro 2A cells but has no effect on their function, we have further confirmed the significance of uPAR-alpha5beta1 interaction. CONCLUSION: Taken together, we report evidence pointing to an important role of uPAR, rather than uPA, in peripheral nerve recovery and neuritogenesis. |
