Dysregulation of Tweak and Fn14 in skeletal muscle of spinal muscular atrophy mice.
Atrophy
Denervation
Fn14
Glucose metabolism
Skeletal muscle
Smn
Spinal muscular atrophy
Survival motor neuron
Tweak
Journal
Skeletal muscle
ISSN: 2044-5040
Titre abrégé: Skelet Muscle
Pays: England
ID NLM: 101561193
Informations de publication
Date de publication:
28 07 2022
28 07 2022
Historique:
received:
13
09
2021
accepted:
10
07
2022
entrez:
28
7
2022
pubmed:
29
7
2022
medline:
2
8
2022
Statut:
epublish
Résumé
Spinal muscular atrophy (SMA) is a childhood neuromuscular disorder caused by depletion of the survival motor neuron (SMN) protein. SMA is characterized by the selective death of spinal cord motor neurons, leading to progressive muscle wasting. Loss of skeletal muscle in SMA is a combination of denervation-induced muscle atrophy and intrinsic muscle pathologies. Elucidation of the pathways involved is essential to identify the key molecules that contribute to and sustain muscle pathology. The tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/TNF receptor superfamily member fibroblast growth factor-inducible 14 (Fn14) pathway has been shown to play a critical role in the regulation of denervation-induced muscle atrophy as well as muscle proliferation, differentiation, and metabolism in adults. However, it is not clear whether this pathway would be important in highly dynamic and developing muscle. We thus investigated the potential role of the TWEAK/Fn14 pathway in SMA muscle pathology, using the severe Taiwanese Smn Here, we report significantly dysregulated expression of Tweak, Fn14, and previously proposed downstream effectors during disease progression in skeletal muscle of the two SMA mouse models. In addition, siRNA-mediated Smn knockdown in C2C12 myoblasts suggests a genetic interaction between Smn and the TWEAK/Fn14 pathway. Further analyses of SMA, Tweak Our study provides mechanistic insights into potential molecular players that contribute to muscle pathology in SMA and into likely differential responses of the TWEAK/Fn14 pathway in developing muscle.
Sections du résumé
BACKGROUND
Spinal muscular atrophy (SMA) is a childhood neuromuscular disorder caused by depletion of the survival motor neuron (SMN) protein. SMA is characterized by the selective death of spinal cord motor neurons, leading to progressive muscle wasting. Loss of skeletal muscle in SMA is a combination of denervation-induced muscle atrophy and intrinsic muscle pathologies. Elucidation of the pathways involved is essential to identify the key molecules that contribute to and sustain muscle pathology. The tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/TNF receptor superfamily member fibroblast growth factor-inducible 14 (Fn14) pathway has been shown to play a critical role in the regulation of denervation-induced muscle atrophy as well as muscle proliferation, differentiation, and metabolism in adults. However, it is not clear whether this pathway would be important in highly dynamic and developing muscle.
METHODS
We thus investigated the potential role of the TWEAK/Fn14 pathway in SMA muscle pathology, using the severe Taiwanese Smn
RESULTS
Here, we report significantly dysregulated expression of Tweak, Fn14, and previously proposed downstream effectors during disease progression in skeletal muscle of the two SMA mouse models. In addition, siRNA-mediated Smn knockdown in C2C12 myoblasts suggests a genetic interaction between Smn and the TWEAK/Fn14 pathway. Further analyses of SMA, Tweak
CONCLUSIONS
Our study provides mechanistic insights into potential molecular players that contribute to muscle pathology in SMA and into likely differential responses of the TWEAK/Fn14 pathway in developing muscle.
Identifiants
pubmed: 35902978
doi: 10.1186/s13395-022-00301-z
pii: 10.1186/s13395-022-00301-z
pmc: PMC9331072
doi:
Substances chimiques
Cytokine TWEAK
0
RNA, Small Interfering
0
Receptors, Tumor Necrosis Factor
0
TWEAK Receptor
0
Tnfrsf12a protein, mouse
0
Tnfsf12 protein, mouse
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
18Subventions
Organisme : Academy of Medical Sciences
ID : SBF006/1162
Pays : United Kingdom
Organisme : CIHR
Pays : Canada
Informations de copyright
© 2022. The Author(s).
Références
JAMA Neurol. 2015 Jun;72(6):666-75
pubmed: 25844556
J Biol Chem. 2003 Mar 7;278(10):8826-36
pubmed: 12477723
Nature. 1977 Dec 22-29;270(5639):725-7
pubmed: 563524
Hum Mol Genet. 2015 Jun 15;24(12):3440-56
pubmed: 25765661
J Biol Chem. 1999 Nov 12;274(46):33166-76
pubmed: 10551889
J Clin Invest. 2014 Feb;124(2):785-800
pubmed: 24463453
Natl Vital Stat Rep. 2010 Dec;59(2):1-52
pubmed: 25073655
Neuropathol Appl Neurobiol. 1994 Oct;20(5):495-500
pubmed: 7845535
Cell Immunol. 2012;272(2):293-8
pubmed: 22055894
Physiol Rev. 2013 Jan;93(1):23-67
pubmed: 23303905
J Neuromuscul Dis. 2016 Aug 30;3(3):293-308
pubmed: 27854229
Neuroscience. 2010 Dec 29;171(4):1256-64
pubmed: 20955770
J Neuropathol Exp Neurol. 2014 Jun;73(6):559-67
pubmed: 24806300
J Neuropathol Exp Neurol. 2009 May;68(5):474-81
pubmed: 19525895
EBioMedicine. 2018 May;31:226-242
pubmed: 29735415
Mol Med Rep. 2018 Jan;17(1):1998-2004
pubmed: 29257217
J Immunol. 2006 Feb 1;176(3):1889-98
pubmed: 16424220
JCI Insight. 2017 Mar 9;2(5):e89970
pubmed: 28289706
Curr Opin Clin Nutr Metab Care. 2012 May;15(3):233-9
pubmed: 22366923
J Clin Invest. 2005 Sep;115(9):2330-40
pubmed: 16110324
Sci Rep. 2016 Jun 28;6:28846
pubmed: 27349908
Hum Mol Genet. 2017 Oct 1;26(R2):R151-R159
pubmed: 28977438
J Biol Chem. 2009 Feb 13;284(7):4439-50
pubmed: 19074147
Exp Cell Res. 2005 Nov 15;311(1):49-61
pubmed: 16219305
Neuromuscul Disord. 2012 Mar;22(3):263-76
pubmed: 22071333
Front Physiol. 2013 Dec 18;4:356
pubmed: 24391590
Skelet Muscle. 2013 Oct 11;3(1):24
pubmed: 24119341
J Cell Biol. 2010 Mar 22;188(6):833-49
pubmed: 20308426
Ann Med. 2006;38(6):389-402
pubmed: 17008303
Hum Mol Genet. 2014 Jul 1;23(13):3432-44
pubmed: 24497575
Methods Mol Biol. 2016;1460:61-71
pubmed: 27492166
Cell. 1995 Jan 13;80(1):155-65
pubmed: 7813012
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
Hum Mol Genet. 2016 Oct 15;25(20):4494-4506
pubmed: 28172892
FASEB J. 2011 Apr;25(4):1306-13
pubmed: 21228222
Int J Mol Sci. 2021 May 31;22(11):
pubmed: 34072857
Sci Rep. 2019 Feb 7;9(1):1633
pubmed: 30733501
Curr Opin Genet Dev. 2008 Oct;18(5):426-34
pubmed: 18782618
Hum Mol Genet. 2010 Apr 15;19(8):1468-78
pubmed: 20097679
FASEB J. 2014 Mar;28(3):1398-411
pubmed: 24327607
Hum Mol Genet. 2009 Nov 1;18(21):4035-45
pubmed: 19648294
J Physiol. 2019 Sep;597(18):4757-4778
pubmed: 31361024
Front Immunol. 2014 Feb 18;5:63
pubmed: 24600451
J Cell Biol. 2007 Mar 12;176(6):831-41
pubmed: 17353360
Hum Mol Genet. 2010 Apr 15;19(8):1492-506
pubmed: 20097677
Biochim Biophys Acta Mol Cell Res. 2017 May;1864(5):760-770
pubmed: 28214532
Muscle Nerve. 1985 Feb;8(2):132-7
pubmed: 2932637
BMC Med. 2012 Mar 07;10:24
pubmed: 22397316
Sci Signal. 2012 Mar 20;5(216):ra22
pubmed: 22434933
Nucleic Acids Res. 2001 May 1;29(9):e45
pubmed: 11328886
Hum Mol Genet. 2014 Aug 15;23(16):4249-59
pubmed: 24691550
PLoS One. 2008;3(10):e3614
pubmed: 18974883
Ann Neurol. 2012 Aug;72(2):256-68
pubmed: 22926856
Nat Genet. 2000 Jan;24(1):66-70
pubmed: 10615130
J Burn Care Res. 2013 Sep-Oct;34(5):e297-304
pubmed: 23816995
Proc Natl Acad Sci U S A. 2013 Oct 8;110(41):16474-9
pubmed: 24065826
Science. 2001 Nov 23;294(5547):1704-8
pubmed: 11679633
Neurobiol Dis. 1996 Apr;3(2):97-110
pubmed: 9173917
Circulation. 2009 Apr 21;119(15):2058-68
pubmed: 19349318
J Neurol Sci. 2008 Dec 15;275(1-2):117-20
pubmed: 18793781
Ann Neurol. 2005 May;57(5):704-12
pubmed: 15852397
Front Immunol. 2014 Jan 27;5:18
pubmed: 24478779
Cell Mol Life Sci. 2020 Sep;77(17):3369-3381
pubmed: 32200423
J Neurosci Res. 2009 Sep;87(12):2748-56
pubmed: 19437551
J Biol Chem. 2007 May 18;282(20):15000-10
pubmed: 17383968
EMBO J. 2006 Dec 13;25(24):5826-39
pubmed: 17124496
Nucleic Acids Res. 2017 Jan 4;45(D1):D362-D368
pubmed: 27924014
FASEB J. 2018 Apr;32(4):1741-1777
pubmed: 29242278
FASEB J. 2015 Mar;29(3):988-1002
pubmed: 25466899
Neurotherapeutics. 2016 Jan;13(1):198-216
pubmed: 26582176
Biochem Biophys Res Commun. 2004 Jan 23;313(4):856-62
pubmed: 14706621
Pharmacol Res. 2018 Apr;130:123-126
pubmed: 29288718
Proc Natl Acad Sci U S A. 1999 Feb 2;96(3):1042-7
pubmed: 9927690
Exp Neurol. 2007 Sep;207(1):64-74
pubmed: 17628540
J Clin Immunol. 2011 Oct;31(5):848-56
pubmed: 21691937
PLoS Genet. 2017 Apr 20;13(4):e1006744
pubmed: 28426667
Hum Mol Genet. 2012 Jan 1;21(1):185-95
pubmed: 21968514
Cell Death Differ. 2015 Feb;22(2):248-57
pubmed: 25323588
Dev Dyn. 1992 Jul;194(3):209-21
pubmed: 1467557
Am J Pathol. 2010 Oct;177(4):1732-42
pubmed: 20724600
Front Immunol. 2014 Feb 05;5:34
pubmed: 24550918
Hum Mol Genet. 2011 Nov 15;20(22):4334-44
pubmed: 21840928