Urokinase receptor regulates nerve regeneration through its interaction with α5β1 integrin

Klimovich, P.S.; Semina, E.V.; Karagyaur, M.N.; Rysenkova, K.D.; Sysoeva, V.Y.; Mironov, N.A.; Sagaradze, G.D.; Az'muko, A.A.; Popov, V.S.; Rubina, K.A.; Tkachuk, V.A.

Статья опубликована в высокорейтинговом журнале

Информация о цитировании статьи получена из Web of Science, Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 29 апреля 2020 г.

Авторы: Klimovich P.S., Semina E.V., Karagyaur M.N., Rysenkova K.D., Sysoeva V.Yu, Mironov N.A., Sagaradze G.D., Az'muko A.A., Popov V.S., Rubina K.A., Tkachuk V.A.
Журнал: Biomedicine and Pharmacotherapy
Том: 125
Год издания: 2020
Издательство: Elsevier BV
Местоположение издательства: Netherlands
Номер статьи: 110008
DOI: 10.1016/j.biopha.2020.110008
Аннотация: Purpose. Urokinase receptor (uPAR) promotes extracellular matrix proteolysis,regulates adhesion and cell migration, transduces intracellular signals through interactionswith the lateral partners. The expression of uPAR and urokinase (uPA) is significantlyupregulated in peripheral nerves after injury, however, little is known about uPAR functionin nerve regeneration or the molecular mechanisms involved. The purpose of this study isto investigate the role of uPAR in nerve regeneration after traumatic injury of n. Peroneuscommunis in uPA-/-, uPAR-/- or control mice (WT) and in neuritogenesis in an in vitroNeuro 2A cell model.Results. Electrophysiological analysis indicates that nerve recovery is significantlyimpaired in uPAR-/- mice, but not in uPA-/- mice. These data correlate with the reducedamount of NF200-positive axons in regenerating nerves from uPAR-/- mice compared touPA-/- or control mice. There is an increase in uPAR expression and remarkablecolocalization 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 invitro model of neuritogenesis and α325 blocking peptide, which abrogates uPAR-α5β1interaction in Neuro 2A cells but has no effect on their function, we have further confirmedthe significance of uPAR-α5β1 interaction.Conclusion.Taken together, we report evidence pointing to an important role ofuPAR, rather than uPA, in peripheral nerve recovery and neuritogenesis.
Добавил в систему: Семина Екатерина Владимировна

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