Urokinase receptor regulates nerve regeneration through its interaction with α5β1-integrin

Klimovich, Polina S.; Semina, Ekaterina V.; Karagyaur, Maxim; Rysenkova, Karina D.; Sysoeva, Veronika; Mironov, N.A.; Sagaradze, Georgy; Азьмуко, А. А.; Попов, В. С.; Рубина, К. А.; Ткачук, В. А.

doi:10.1016/j.biopha.2020.110008

Cited by 15 publications

(14 citation statements)

References 58 publications

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“…Using an in vivo model, we have demonstrated that the increase in α5β1 integrin expression is a key feature of peripheral nerve regeneration after injury. Our in vitro experiments revealed that the increase in α5β1 integrin expression stimulates neuritogenesis, while α5β1 integrin inhibition disrupts neurite outgrowth on fibronectin matrix [26]. The interactions between ECM substrates and integrin receptors alter the intracellular level of second messengers (cAMP) in the growth cone resulting in activation of downstream effector proteins such as focal adhesion kinase (FAK) and integrin-linked kinase (ILK), which further activate small GTPases, leading to cytoskeleton remodeling and an increased mobility of the growth cone [25].…”

Section: Cell Adhesion Molecules and Extracellular Matrix Proteins In Peripheral Nerve Regenerationmentioning

confidence: 70%

New Frontiers in Peripheral Nerve Regeneration: Concerns and Remedies

Klimovich

Рубина

Semina

2021

IJMS

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Topical advances in studying molecular and cellular mechanisms responsible for regeneration in the peripheral nervous system have highlighted the ability of the nervous system to repair itself. Still, serious injuries represent a challenge for the morphological and functional regeneration of peripheral nerves, calling for new treatment strategies that maximize nerve regeneration and recovery. This review presents the canonical view of the basic mechanisms of nerve regeneration and novel data on the role of exosomes and their transferred microRNAs in intracellular communication, regulation of axonal growth, Schwann cell migration and proliferation, and stromal cell functioning. An integrated comprehensive understanding of the current mechanistic underpinnings will open the venue for developing new clinical strategies to ensure full regeneration in the peripheral nervous system.

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Section: Cell Adhesion Molecules and Extracellular Matrix Proteins In Peripheral Nerve Regenerationmentioning

confidence: 70%

New Frontiers in Peripheral Nerve Regeneration: Concerns and Remedies

Klimovich

Рубина

Semina

2021

IJMS

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“…The binding process of the urokinase receptor and integrin mediates the processes of regulating cell adhesion, intercell signal transmission and axonal regeneration after injury in the central nervous system. [59]. Integrin-linked kinase (ILK) is also involved in the nerve growth factor-mediated postinjury repair of nerve fibers and binding in the PI3K/Akt pathway [60].…”

Section: Discussionmentioning

confidence: 99%

Urine proteome changes in a chronic unpredictable mild stress (CUMS) mouse model of major depressive disorder

Huan

Wei

et al. 2021

Journal of Pharmaceutical and Biomedical Analysis

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Background. Major depressive disorder (MDD) is a prevalent complex psychiatric disorder with a high prevalence rate. Because MDD is a systemic multifactorial disorder involving complex interactions and disturbances of various molecular pathways, there are no effective biomarkers for clinical diagnosis. Urine is not subjected to homeostatic control, allowing it to reflect the sensitive and comprehensive changes that occur in various diseases. In this study, we examined the urine proteome changes in a CUMS mouse model of MDD. Methods. Male C57BL/6 mice were subjected to chronic unpredictable mild stress for 5 weeks. The tail suspension test (TST) and sucrose consumption test (SCT) were then applied to evaluate depression-like behaviors. The urine proteomes on day 0 and day 36 in the CUMS group were profiled by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Results. A total of 45 differential proteins were identified, 24 of which have been associated with the pathogenic mechanisms of MDD, while 10 proteins have been previously suggested as MDD biomarkers. There was an average of two differential proteins that were identified through 1048574 random combination statistical analyses, indicating that at least 95% of the differential proteins were reliable and not the result of random combination. The differential proteins were mainly associated with blood coagulation, inflammatory responses and central nervous system development. Conclusions. Our preliminary results indicated that the urine proteome can reflect changes associated with MDD in the CUMS model, which provides potential clues for the diagnosis of clinical MDD patients.

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“…Increase SC migration and wrapping of nerve fibers [85] tPA and uPA promote nerve regeneration after injury [86,87] Canonical and noncanonical…”

Section: Plasminmentioning

confidence: 99%

“…Low levels, increased release of neurotrophic factors [13] Low levels, enhanced regeneration [10] Canonical High levels, decreased SC neurotrophic activity [80] High levels, reduced regeneration [11] FXa Increased release of thrombin in a Schwannoma cell line [9] Inhibition of FXa restores motor function after injury [9] Canonical FVIIa Expressed in a Schwannoma cell line [9] Expressed at the nodes of Ranvier [9] Canonical APC/EPCR EPCR expression in a Schwannoma cell line [7] EPCR increased expression after crush injury [7] Canonical and noncanonical Plasmin Increase SC migration and wrapping of nerve fibers [85] tPA and uPA promote nerve regeneration after injury [86,87] Canonical and noncanonical MMPs Inhibit SC proliferation [88] Inhibit nerve regeneration [89] Canonical and noncanonical…”

Section: Thrombinmentioning

confidence: 99%

“…Furthermore, in the PNS, both the neurons and SCs express uPA, whose level increases after damage during the early stages of regeneration (1–7 days after injury) in peripheral nerves in vivo and in sensory neurons in vitro [ 87 , 105 , 106 , 107 , 108 ]. Therefore, both the tPA and uPA mediate an extracellular proteolytic cascade that seems to play a protective role against axonal degradation and demyelination, and to promote axonal regeneration after sciatic nerve crush [ 87 ].…”

Section: Plasmin In Peripheral Nerve Injurymentioning

confidence: 99%

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Protease Activated Receptor 1 and Its Ligands as Main Regulators of the Regeneration of Peripheral Nerves

et al. 2021

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In contrast with the brain and spinal cord, peripheral nerves possess a striking ability to regenerate after damage. This characteristic of the peripheral nervous system is mainly due to a specific population of glial cells, the Schwann cells. Schwann cells promptly activate after nerve injury, dedifferentiate assuming a repair phenotype, and assist axon regrowth. In general, tissue injury determines the release of a variety of proteases which, in parallel with the degradation of their specific targets, also activate plasma membrane receptors known as protease-activated receptors (PARs). PAR1, the prototypical member of the PAR family, is also known as thrombin receptor and is present at the Schwann cell plasma membrane. This receptor is emerging as a possible regulator of the pro-regenerative capacity of Schwann cells. Here, we summarize the most recent literature data describing the possible contribution of PAR1 and PAR1-activating proteases in regulating the regeneration of peripheral nerves.

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Urokinase receptor regulates nerve regeneration through its interaction with α5β1-integrin

Cited by 15 publications

References 58 publications

New Frontiers in Peripheral Nerve Regeneration: Concerns and Remedies

New Frontiers in Peripheral Nerve Regeneration: Concerns and Remedies

Urine proteome changes in a chronic unpredictable mild stress (CUMS) mouse model of major depressive disorder

Protease Activated Receptor 1 and Its Ligands as Main Regulators of the Regeneration of Peripheral Nerves

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