Neuritin accelerates Schwann cell dedifferentiation via PI3K/Akt/mTOR signalling pathway during Wallerian degeneration.
Schwann Cells
/ metabolism
Wallerian Degeneration
/ metabolism
Animals
Cell Dedifferentiation
TOR Serine-Threonine Kinases
/ metabolism
Signal Transduction
Proto-Oncogene Proteins c-akt
/ metabolism
Phosphatidylinositol 3-Kinases
/ metabolism
Neuropeptides
/ metabolism
Sciatic Nerve
/ injuries
GPI-Linked Proteins
/ metabolism
Rats
Peripheral Nerve Injuries
/ metabolism
Rats, Sprague-Dawley
Axons
/ metabolism
Male
Phagocytosis
Mice
Neuritin
Schwann cells
Wallerian degeneration
dedifferentiation
demyelination
mTOR
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
Aug 2024
Aug 2024
Historique:
revised:
08
07
2024
received:
19
05
2024
accepted:
05
08
2024
medline:
27
8
2024
pubmed:
27
8
2024
entrez:
26
8
2024
Statut:
ppublish
Résumé
Neuritin, also known as candidate plasticity gene 15 (CPG15), was first identified as one of the activity-dependent gene products in the brain. Previous studies have been reported that Neuritin induces neuritogenesis, neurite arborization, neurite outgrowth and synapse formation, which are involved in the development and functions of the central nervous system. However, the role of Neuritin in peripheral nerve injury is still unknown. Given the importance and necessity of Schwann cell dedifferentiation response to peripheral nerve injury, we aim to investigate the molecular mechanism of Neuritin steering Schwann cell dedifferentiation during Wallerian degeneration (WD) in injured peripheral nerve. Herein, using the explants of sciatic nerve, an ex vivo model of nerve degeneration, we provided evidences indicating that Neuritin vividly accelerates Schwann cell dedifferentiation. Moreover, we found that Neuritin promotes Schwann cell demyelination as well as axonal degeneration, phagocytosis, secretion capacity. In summary, we first described Neuritin acts as a positive regulator for Schwann cell dedifferentiation and WD after peripheral nerve injury.
Substances chimiques
TOR Serine-Threonine Kinases
EC 2.7.11.1
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Phosphatidylinositol 3-Kinases
EC 2.7.1.-
Neuropeptides
0
GPI-Linked Proteins
0
Nrn1 protein, rat
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e70012Subventions
Organisme : National Key R&D Program of China
ID : 2022YFC2502901
Organisme : President Foundation of Nanfang Hospital, Southern Medical University
ID : 2023A039
Informations de copyright
© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
Références
Zhao QR, Lu JM, Li ZY, Mei YA. Neuritin promotes neurite and spine growth in rat cerebellar granule cells via L‐type calcium channel‐mediated calcium influx. J Neurochem. 2018;147(1):40‐57. doi:10.1111/jnc.14535
Naeve GS, Ramakrishnan M, Kramer R, Hevroni D, Citri Y, Theill LE. Neuritin: a gene induced by neural activity and neurotrophins that promotes neuritogenesis. Proc Natl Acad Sci USA. 1997;94(6):2648‐2653. doi:10.1073/pnas.94.6.2648
Karamoysoyli E, Burnand RC, Tomlinson DR, Gardiner NJ. Neuritin mediates nerve growth factor‐induced axonal regeneration and is deficient in experimental diabetic neuropathy. Diabetes. 2008;57(1):181‐189. doi:10.2337/db07-0895
Xi C, Zhang Y, Yan M, et al. Exogenous neuritin treatment improves survivability and functions of Schwann cells with improved outgrowth of neurons in rat diabetic neuropathy. J Cell Mol Med. 2020;24(17):10166‐10176. doi:10.1111/jcmm.15627
Huang T, Li H, Zhang S, Liu F, Wang D, Xu J. Nrn1 overexpression attenuates retinal ganglion cell apoptosis, promotes axonal regeneration, and improves visual function following optic nerve crush in rats. J Mol Neurosci. 2021;71(1):66‐79. doi:10.1007/s12031-020-01627-3
Li X, Zhang T, Li C, et al. Electrical stimulation accelerates Wallerian degeneration and promotes nerve regeneration after sciatic nerve injury. Glia. 2023;71(3):758‐774. doi:10.1002/glia.24309
Liu J, Li L, Zou Y, et al. Role of microtubule dynamics in Wallerian degeneration and nerve regeneration after peripheral nerve injury. Neural Regen Res. 2022;17(3):673‐681. doi:10.4103/1673-5374.320997
Zou Y, Zhang J, Liu J, et al. SIRT6 negatively regulates Schwann cells dedifferentiation via targeting c‐Jun during Wallerian degeneration after peripheral nerve injury. Mol Neurobiol. 2022;59(1):429‐444. doi:10.1007/s12035-021-02607-3
Xu J, Wen J, Fu L, et al. Macrophage‐specific RhoA knockout delays Wallerian degeneration after peripheral nerve injury in mice. J Neuroinflammation. 2021;18(1):234. doi:10.1186/s12974-021-02292-y
Lee SH, Kim NS, Choi M, et al. LGI1 governs Neuritin‐mediated resilience to chronic stress. Neurobiol Stress. 2021;15:100373. doi:10.1016/j.ynstr.2021.100373
Yao JJ, Gao XF, Chow CW, Zhan XQ, Hu CL, Mei YA. Neuritin activates insulin receptor pathway to up‐regulate Kv4.2‐mediated transient outward K+ current in rat cerebellar granule neurons. J Biol Chem. 2012;287(49):41534‐41545. doi:10.1074/jbc.M112.390260
Guo J, Wang L, Zhang Y, et al. Abnormal junctions and permeability of myelin in PMP22‐deficient nerves. Ann Neurol. 2014;75(2):255‐265. doi:10.1002/ana.24086
Jung J, Cai W, Lee HK, et al. Actin polymerization is essential for myelin sheath fragmentation during Wallerian degeneration. J Neurosci. 2011;31(6):2009‐2015. doi:10.1523/JNEUROSCI.4537-10.2011
Zou Y, Wu S, Wen F, Ge Y, Luo S. PGC‐1alpha inhibits Schwann cell dedifferentiation and delays peripheral nerve degeneration by targeting PON1. Cell Mol Neurobiol. 2023;43(7):3767‐3781. doi:10.1007/s10571-023-01395-9
Liu J, Ma X, Hu X, et al. Schwann cell‐specific RhoA knockout accelerates peripheral nerve regeneration via promoting Schwann cell dedifferentiation. Glia. 2023;71(7):1715‐1728. doi:10.1002/glia.24365
Schachner‐Nedherer AL, Werzer O, Kornmueller K, Prassl R, Zimmer A. Biological activity of miRNA‐27a using peptide‐based drug delivery systems. Int J Nanomedicine. 2019;14(14):7795‐7808. doi:10.2147/IJN.S208446
Velickovic K, Lugo LH, Surrati A, et al. Targeting glutamine synthesis inhibits stem cell adipogenesis in vitro. Cell Physiol Biochem. 2020;54(5):917‐927. doi:10.33594/000000278
Li L, Xu Y, Wang X, et al. Ascorbic acid accelerates Wallerian degeneration after peripheral nerve injury. Neural Regen Res. 2021;16(6):1078‐1085. doi:10.4103/1673-5374.300459
Balakrishnan A, Belfiore L, Chu TH, et al. Insights into the role and potential of Schwann cells for peripheral nerve repair from studies of development and injury. Front Mol Neurosci. 2020;13:608442. doi:10.3389/fnmol.2020.608442
Su Q, Nasser MI, He J, et al. Engineered Schwann cell‐based therapies for injury peripheral nerve reconstruction. Front Cell Neurosci. 2022;16:865266. doi:10.3389/fncel.2022.865266
Du W, Gao A, Herman J, et al. Methylation of NRN1 is a novel synthetic lethal marker of PI3K‐Akt‐mTOR and ATR inhibitors in esophageal cancer. Cancer Sci. 2021;112(7):2870‐2883. doi:10.1111/cas.14917
Yao JJ, Zhao QR, Liu DD, Chow CW, Mei YA. Neuritin up‐regulates Kv4.2 alpha‐subunit of potassium channel expression and affects neuronal excitability by regulating the calcium‐calcineurin‐NFATc4 signaling pathway. J Biol Chem. 2016;291(33):17369‐17381. doi:10.1074/jbc.M115.708883
Cheng Q, Wang YX, Yu J, Yi S. Critical signaling pathways during Wallerian degeneration of peripheral nerve. Neural Regen Res. 2017;12(6):995‐1002. doi:10.4103/1673-5374.208596
Park HT, Kim JK, Tricaud N. The conceptual introduction of the "demyelinating Schwann cell" in peripheral demyelinating neuropathies. Glia. 2019;67(4):571‐581. doi:10.1002/glia.23509
Jang SY, Shin YK, Park SY, et al. Autophagic myelin destruction by Schwann cells during Wallerian degeneration and segmental demyelination. Glia. 2016;64(5):730‐742. doi:10.1002/glia.22957
Jia B, Huang W, Wang Y, et al. Nogo‐C inhibits peripheral nerve regeneration by regulating Schwann cell apoptosis and dedifferentiation. Front Neurosci. 2020;14:616258. doi:10.3389/fnins.2020.616258
Elsayed H, Faroni A, Ashraf MR, et al. Development and characterisation of an in vitro model of Wallerian degeneration. Front Bioeng Biotechnol. 2020;8:784. doi:10.3389/fbioe.2020.00784
Jessen KR, Mirsky R. The repair Schwann cell and its function in regenerating nerves. J Physiol‐London. 2016;594(13):3521‐3531. doi:10.1113/JP270874
Pandey S, Mudgal J. A review on the role of endogenous neurotrophins and Schwann cells in axonal regeneration. J Neuroimmune Pharmacol. 2022;17(3–4):398‐408. doi:10.1007/s11481-021-10034-3
Gao D, Huang Y, Sun X, Yang J, Chen J, He J. Overexpression of c‐Jun inhibits erastin‐induced ferroptosis in Schwann cells and promotes repair of facial nerve function. J Cell Mol Med. 2022;26(8):2191‐2204. doi:10.1111/jcmm.17241
Ishii A, Furusho M, Bansal R. Mek/ERK1/2‐MAPK and PI3K/Akt/mTOR signaling plays both independent and cooperative roles in Schwann cell differentiation, myelination and dysmyelination. Glia. 2021;69(10):2429‐2446. doi:10.1002/glia.24049
Yan JN, Zhang HY, Li JR, et al. Schwann cells differentiated from skin‐derived precursors provide neuroprotection via autophagy inhibition in a cellular model of Parkinson's disease. Neural Regen Res. 2022;17(6):1357‐1363. doi:10.4103/1673-5374.327353
Gao D, Tang T, Zhu J, Tang Y, Sun H, Li S. CXCL12 has therapeutic value in facial nerve injury and promotes Schwann cells autophagy and migration via PI3K‐AKT‐mTOR signal pathway. Int J Biol Macromol. 2019;124:460‐468. doi:10.1016/j.ijbiomac.2018.10.212