α7 Nicotinic Acetylcholine Receptors May Improve Schwann Cell Regenerating Potential via Metabotropic Signaling Pathways.
Schwann cells
cell migration
mTORC1
metabotropic signals
α7 nicotinic receptors
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
28 05 2023
28 05 2023
Historique:
received:
06
02
2023
revised:
15
05
2023
accepted:
23
05
2023
medline:
12
6
2023
pubmed:
10
6
2023
entrez:
10
6
2023
Statut:
epublish
Résumé
Schwann cells (SCs) are glial cells involved in peripheral axon myelination. SCs also play a strategic role after peripheral nerve injury, regulating local inflammation and axon regeneration. Our previous studies demonstrated the presence of cholinergic receptors in SCs. In particular, the α7 nicotinic acetylcholine receptors (nAChRs) are expressed in SCs after peripheral axotomy, suggesting their involvement in the regulation of SC-regenerating properties. To clarify the role that α7 nAChRs may play after peripheral axon damage, in this study we investigated the signal transduction pathways triggered by receptor activation and the effects produced by their activation. Both ionotropic and metabotropic cholinergic signaling were analyzed by calcium imaging and Western blot analysis, respectively, following α7 nAChR activation. In addition, the expression of c-Jun and α7 nAChRs was evaluated by immunocytochemistry and Western blot analysis. Finally, the cell migration was studied by a wound healing assay. Activation of α7 nAChRs, activated by the selective partial agonist ICH3, did not induce calcium mobilization but positively modulated the PI3K/AKT/mTORC1 axis. Activation of the mTORC1 complex was also supported by the up-regulated expression of its specific p-p70 S6K Our data demonstrate that α7 nAChRs, expressed by SCs only after peripheral axon damage and/or in an inflammatory microenvironment, contribute to improve the SCs regenerating properties. Indeed, α7 nAChR stimulation leads to an upregulation of c-Jun expression and promotes Schwann cell migration by non-canonical pathways involving the mTORC1 activity.
Sections du résumé
BACKGROUND
Schwann cells (SCs) are glial cells involved in peripheral axon myelination. SCs also play a strategic role after peripheral nerve injury, regulating local inflammation and axon regeneration. Our previous studies demonstrated the presence of cholinergic receptors in SCs. In particular, the α7 nicotinic acetylcholine receptors (nAChRs) are expressed in SCs after peripheral axotomy, suggesting their involvement in the regulation of SC-regenerating properties. To clarify the role that α7 nAChRs may play after peripheral axon damage, in this study we investigated the signal transduction pathways triggered by receptor activation and the effects produced by their activation.
METHODS
Both ionotropic and metabotropic cholinergic signaling were analyzed by calcium imaging and Western blot analysis, respectively, following α7 nAChR activation. In addition, the expression of c-Jun and α7 nAChRs was evaluated by immunocytochemistry and Western blot analysis. Finally, the cell migration was studied by a wound healing assay.
RESULTS
Activation of α7 nAChRs, activated by the selective partial agonist ICH3, did not induce calcium mobilization but positively modulated the PI3K/AKT/mTORC1 axis. Activation of the mTORC1 complex was also supported by the up-regulated expression of its specific p-p70 S6K
CONCLUSIONS
Our data demonstrate that α7 nAChRs, expressed by SCs only after peripheral axon damage and/or in an inflammatory microenvironment, contribute to improve the SCs regenerating properties. Indeed, α7 nAChR stimulation leads to an upregulation of c-Jun expression and promotes Schwann cell migration by non-canonical pathways involving the mTORC1 activity.
Identifiants
pubmed: 37296615
pii: cells12111494
doi: 10.3390/cells12111494
pmc: PMC10253098
pii:
doi:
Substances chimiques
alpha7 Nicotinic Acetylcholine Receptor
0
Calcium
SY7Q814VUP
Phosphatidylinositol 3-Kinases
EC 2.7.1.-
Mechanistic Target of Rapamycin Complex 1
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Références
J Invest Dermatol. 2017 Feb;137(2):e11-e16
pubmed: 28110712
Neuroscience. 2020 May 1;433:94-107
pubmed: 32171817
PLoS One. 2012;7(10):e47977
pubmed: 23110146
Compr Physiol. 2012 Oct;2(4):2369-92
pubmed: 23720251
Front Mol Neurosci. 2017 May 29;10:155
pubmed: 28611586
Mol Neurobiol. 2017 Jul;54(5):3554-3564
pubmed: 27194296
J Neurosci. 2005 Apr 27;25(17):4396-405
pubmed: 15858066
J Neuroimmunol. 2012 Oct 15;251(1-2):65-72
pubmed: 22884467
J Endocrinol Invest. 2020 Jul;43(7):983-993
pubmed: 31965518
Neuron Glia Biol. 2007 Nov;3(4):269-79
pubmed: 18634559
Biomol Concepts. 2017 Sep 26;8(3-4):143-153
pubmed: 28841566
Cold Spring Harb Perspect Biol. 2015 May 08;7(7):a020487
pubmed: 25957303
FEBS J. 2008 Sep;275(17):4343-53
pubmed: 18657190
Molecules. 2021 Dec 18;26(24):
pubmed: 34946750
Int J Mol Sci. 2020 Sep 11;21(18):
pubmed: 32933046
J Neurosci Res. 2006 Jul;84(1):97-105
pubmed: 16634060
J Physiol. 2016 Jul 1;594(13):3521-31
pubmed: 26864683
J Cell Biochem. 2007 Feb 1;100(2):279-92
pubmed: 16888810
J Neurosci. 2016 Apr 20;36(16):4506-21
pubmed: 27098694
J Cell Biol. 2008 May 19;181(4):625-37
pubmed: 18490512
Trends Pharmacol Sci. 2018 Apr;39(4):354-366
pubmed: 29428175
Nat Immunol. 2005 Aug;6(8):844-51
pubmed: 16025117
Mol Cell Biol. 2009 Nov;29(21):5657-70
pubmed: 19720745
Eur J Pharmacol. 2018 Feb 5;820:265-273
pubmed: 29275158
J Neurochem. 2016 Aug;138(4):532-45
pubmed: 27167578
Elife. 2017 Sep 07;6:
pubmed: 28880149
Dev Neurobiol. 2014 Jul;74(7):676-91
pubmed: 24403178
J Neurosci Res. 1996 Mar 01;43(5):511-25
pubmed: 8833086
J Neurosci Res. 1999 May 15;56(4):334-48
pubmed: 10340742
J Clin Invest. 2007 Feb;117(2):289-96
pubmed: 17273548
J Neurosci. 2017 Sep 13;37(37):9086-9099
pubmed: 28904214
Glia. 2021 Oct;69(10):2429-2446
pubmed: 34157170
J Cell Biol. 2012 Jul 9;198(1):127-41
pubmed: 22753894
Neuron. 2016 Oct 19;92(2):316-329
pubmed: 27764665
Biochem Soc Trans. 2013 Aug;41(4):944-50
pubmed: 23863161
Life (Basel). 2022 Jan 29;12(2):
pubmed: 35207498
Int J Mol Sci. 2021 May 06;22(9):
pubmed: 34066354
J Neurosci. 2018 May 16;38(20):4811-4828
pubmed: 29695414
Mol Pharmacol. 1988 Nov;34(5):643-50
pubmed: 3193956
ChemMedChem. 2011 May 2;6(5):889-903
pubmed: 21365765
Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):4148-53
pubmed: 11259680
Cells Tissues Organs. 2014;200(1):6-12
pubmed: 25765065
ACS Med Chem Lett. 2017 Sep 26;8(10):989-991
pubmed: 29057037
Front Cell Neurosci. 2019 Feb 11;13:33
pubmed: 30804758
Front Mol Neurosci. 2017 Feb 17;10:38
pubmed: 28261057
Glia. 2021 Feb;69(2):235-254
pubmed: 32697392