Ekaterina Semina1, Kseniya Rubina2, Veronika Sysoeva3, Karina Rysenkova3, Polina Klimovich3, Olga Plekhanova4, Vsevolod Tkachuk1. 1. Department of Biochemistry and Molecular Medicine, Faculty of Medicine, M.V. Lomonosov Moscow State University, Lomonosovsky av. 31/5, 119192 Moscow, Russian Federation; Laboratory of Molecular Endocrinology, Russian Cardiology Research Center, 3rd Cherepkovskaya 15a, 12155 Moscow, Russian Federation. 2. Department of Biochemistry and Molecular Medicine, Faculty of Medicine, M.V. Lomonosov Moscow State University, Lomonosovsky av. 31/5, 119192 Moscow, Russian Federation. Electronic address: rkseniya@mail.ru. 3. Department of Biochemistry and Molecular Medicine, Faculty of Medicine, M.V. Lomonosov Moscow State University, Lomonosovsky av. 31/5, 119192 Moscow, Russian Federation. 4. Laboratory of Molecular Endocrinology, Russian Cardiology Research Center, 3rd Cherepkovskaya 15a, 12155 Moscow, Russian Federation.
Abstract
PURPOSE: Recent findings indicate the significant contribution of urokinase and urokinase receptor (uPA and uPAR) in the processes of nerve regeneration, however, their role in axonal growth and branching is unclear. Using a 3D model of mouse Dorsal Root Ganglia (DRG) explants, differentiated into neurons Neuro 2a cells and transgenic mice lacking the urokinase gene, we studied the involvement of the uPA/uPAR system in the neural cell migration, neurite outgrowth, elongation and branching. RESULTS: uPA and uPAR are expressed in the growth cones of axons. Using an ex vivo model of DRG explants in Matrigel we have found that uPA inhibition attenuates neural cell migration and axonal growth, pointing to an important role of urokinase in these processes. Apparently, uPA mediates its effects through its specific receptor uPAR: anti-uPAR antibody, which blocks the uPA binding to uPAR, stimulates axon branching and attenuates neural cell migration from DRG explants. Simultaneous inhibition of uPA and uPAR almost completely prevents the axonal outgrowth from explants into the Matrigels. Experiments in vitro using Neuro 2a cells differentiated into neurons demonstrate that administration of exogenous uPA increases the neurite growth rate (elongation), most likely via the interaction of uPA with uPAR. Blocking of uPAR stimulates neurite formation and enhances branching of preexisting neurites. The results obtained on DRG explants from transgenic mice lacking uPA gene support the assumption that uPA stimulates neurite growth via uPA/uPAR interaction and uPAR role in axons branching and neural cell migration. CONCLUSIONS: The uPA/uPAR system plays an essential role in neural cell migration, axonal growth and branching.
PURPOSE: Recent findings indicate the significant contribution of urokinase and urokinase receptor (uPA and uPAR) in the processes of nerve regeneration, however, their role in axonal growth and branching is unclear. Using a 3D model of mouse Dorsal Root Ganglia (DRG) explants, differentiated into neurons Neuro 2a cells and transgenic mice lacking the urokinase gene, we studied the involvement of the uPA/uPAR system in the neural cell migration, neurite outgrowth, elongation and branching. RESULTS:uPA and uPAR are expressed in the growth cones of axons. Using an ex vivo model of DRG explants in Matrigel we have found that uPA inhibition attenuates neural cell migration and axonal growth, pointing to an important role of urokinase in these processes. Apparently, uPA mediates its effects through its specific receptor uPAR: anti-uPAR antibody, which blocks the uPA binding to uPAR, stimulates axon branching and attenuates neural cell migration from DRG explants. Simultaneous inhibition of uPA and uPAR almost completely prevents the axonal outgrowth from explants into the Matrigels. Experiments in vitro using Neuro 2a cells differentiated into neurons demonstrate that administration of exogenous uPA increases the neurite growth rate (elongation), most likely via the interaction of uPA with uPAR. Blocking of uPAR stimulates neurite formation and enhances branching of preexisting neurites. The results obtained on DRG explants from transgenic mice lacking uPA gene support the assumption that uPA stimulates neurite growth via uPA/uPAR interaction and uPAR role in axons branching and neural cell migration. CONCLUSIONS: The uPA/uPAR system plays an essential role in neural cell migration, axonal growth and branching.
Authors: Ekaterina V Semina; Kseniya A Rubina; Anna A Shmakova; Karina D Rysenkova; Polina S Klimovich; Natalya A Aleksanrushkina; Veronika Y Sysoeva; Maxim N Karagyaur; Vsevolod A Tkachuk Journal: J Cell Physiol Date: 2020-01-28 Impact factor: 6.384
Authors: V M Baart; R D Houvast; L F de Geus-Oei; P H A Quax; P J K Kuppen; A L Vahrmeijer; C F M Sier Journal: EJNMMI Res Date: 2020-07-28 Impact factor: 3.138
Authors: Karina D Rysenkova; Ekaterina V Semina; Maxim N Karagyaur; Anna A Shmakova; Daniyar T Dyikanov; Petr A Vasiluev; Yury P Rubtsov; Kseniya A Rubina; Vsevolod A Tkachuk Journal: Oncotarget Date: 2018-06-29