Resolvin-D2 targets myogenic cells and improves muscle regeneration in Duchenne muscular dystrophy.
Animals
Cell Differentiation
/ drug effects
Cells, Cultured
Disease Models, Animal
Docosahexaenoic Acids
/ pharmacology
Glucocorticoids
/ pharmacology
Macrophages
/ drug effects
Male
Mice, Inbred mdx
Mice, Knockout
Muscle Contraction
/ drug effects
Muscle Development
/ drug effects
Muscular Dystrophy, Duchenne
/ drug therapy
Myoblasts
/ drug effects
Utrophin
/ genetics
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
29 10 2021
29 10 2021
Historique:
received:
10
07
2020
accepted:
29
09
2021
entrez:
30
10
2021
pubmed:
31
10
2021
medline:
1
12
2021
Statut:
epublish
Résumé
Lack of dystrophin causes muscle degeneration, which is exacerbated by chronic inflammation and reduced regenerative capacity of muscle stem cells in Duchenne Muscular Dystrophy (DMD). To date, glucocorticoids remain the gold standard for the treatment of DMD. These drugs are able to slow down the progression of the disease and increase lifespan by dampening the chronic and excessive inflammatory process; however, they also have numerous harmful side effects that hamper their therapeutic potential. Here, we investigated Resolvin-D2 as a new therapeutic alternative having the potential to target multiple key features contributing to the disease progression. Our in vitro findings showed that Resolvin-D2 promotes the switch of macrophages toward their anti-inflammatory phenotype and increases their secretion of pro-myogenic factors. Moreover, Resolvin-D2 directly targets myogenic cells and promotes their differentiation and the expansion of the pool of myogenic progenitor cells leading to increased myogenesis. These effects are ablated when the receptor Gpr18 is knocked-out, knocked-down, or blocked by the pharmacological antagonist O-1918. Using different mouse models of DMD, we showed that Resolvin-D2 targets both inflammation and myogenesis leading to enhanced muscle function compared to glucocorticoids. Overall, this preclinical study has identified a new therapeutic approach that is more potent than the gold-standard treatment for DMD.
Identifiants
pubmed: 34716330
doi: 10.1038/s41467-021-26516-0
pii: 10.1038/s41467-021-26516-0
pmc: PMC8556273
doi:
Substances chimiques
Glucocorticoids
0
Utrophin
0
resolvin D2
0
Docosahexaenoic Acids
25167-62-8
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6264Subventions
Organisme : CIHR
ID : PJT-156408
Pays : Canada
Informations de copyright
© 2021. The Author(s).
Références
Cell Stem Cell. 2019 Mar 7;24(3):419-432.e6
pubmed: 30713094
Sci Transl Med. 2015 Aug 5;7(299):299rv4
pubmed: 26246170
Front Immunol. 2019 May 24;10:1084
pubmed: 31178859
BMC Neurosci. 2010 Mar 26;11:44
pubmed: 20346144
Int J Mol Sci. 2018 Mar 31;19(4):
pubmed: 29614751
Stem Cells Transl Med. 2016 Jan;5(1):20-32
pubmed: 26607175
Cell Rep. 2018 Nov 20;25(8):2163-2176.e6
pubmed: 30463013
J Immunol. 2012 Oct 1;189(7):3669-80
pubmed: 22933625
Clin Immunol. 2001 Feb;98(2):235-43
pubmed: 11161980
Int J Neuropsychopharmacol. 2017 Jul 1;20(7):575-584
pubmed: 28419244
Development. 2015 May 1;142(9):1572-81
pubmed: 25922523
Immunity. 2014 Mar 20;40(3):315-27
pubmed: 24656045
Neuromuscul Disord. 2000 Jun;10(4-5):276-82
pubmed: 10838255
Elife. 2020 Feb 03;9:
pubmed: 32011235
Muscle Nerve. 2009 Sep;40(3):443-54
pubmed: 19618428
PLoS One. 2013;8(3):e58554
pubmed: 23516508
Cell. 2010 Dec 23;143(7):1059-71
pubmed: 21145579
Nat Commun. 2021 Feb 2;12(1):750
pubmed: 33531466
Cell Stem Cell. 2016 Dec 1;19(6):800-807
pubmed: 27641304
Proc Natl Acad Sci U S A. 1984 Feb;81(4):1189-92
pubmed: 6583703
Int J Biochem Cell Biol. 2013 Oct;45(10):2163-72
pubmed: 23806868
J Exp Med. 2015 Jul 27;212(8):1203-17
pubmed: 26195725
Front Immunol. 2019 Feb 26;10:307
pubmed: 30863409
Dis Model Mech. 2020 Feb 21;13(2):
pubmed: 32224495
JCI Insight. 2020 Sep 17;5(18):
pubmed: 32750044
PLoS One. 2015 Dec 23;10(12):e0145342
pubmed: 26699615
Mol Pharmacol. 2003 Mar;63(3):699-705
pubmed: 12606780
Nat Chem Biol. 2010 Jun;6(6):411-7
pubmed: 20436487
Stem Cells. 2019 Dec;37(12):1615-1628
pubmed: 31574188
ACS Nano. 2018 Dec 26;12(12):12140-12148
pubmed: 30457830
Nat Commun. 2015 Sep 16;6:8272
pubmed: 26374165
Br J Dermatol. 2013 Jan;168(1):172-8
pubmed: 22834636
Cochrane Database Syst Rev. 2008 Jan 23;(1):CD003725
pubmed: 18254031
Nature. 2009 Oct 29;461(7268):1287-91
pubmed: 19865173
Cell. 2003 May 16;113(4):483-94
pubmed: 12757709
JCI Insight. 2016 Apr 21;1(5):e85922
pubmed: 27158677
Am J Pathol. 2013 Feb;182(2):505-15
pubmed: 23201131
J Neuromuscul Dis. 2018;5(1):29-34
pubmed: 29480217
Circulation. 2016 Aug 30;134(9):666-680
pubmed: 27507404
Cell Rep. 2016 Jun 7;15(10):2301-2312
pubmed: 27239027
Lab Invest. 2013 Sep;93(9):991-1000
pubmed: 23857007
J Pharmacol Exp Ther. 2014 Apr;349(1):29-38
pubmed: 24431468
Neuromuscul Disord. 2006 Oct;16(9-10):591-602
pubmed: 16935507
Cell Metab. 2013 Aug 6;18(2):251-64
pubmed: 23931756
Lab Invest. 1984 Feb;50(2):197-207
pubmed: 6694359
Mol Biol Rep. 2000 Jun;27(2):87-98
pubmed: 11092555
Ann Neurol. 2012 Mar;71(3):304-13
pubmed: 22451200
J Pathol. 2016 Dec;240(4):410-424
pubmed: 27569721
Expert Opin Emerg Drugs. 2012 Jun;17(2):261-77
pubmed: 22632414
NPJ Regen Med. 2016;1:
pubmed: 29188075
Methods Mol Biol. 2018;1686:149-159
pubmed: 29030819
Br J Pharmacol. 2013 Jun;169(4):834-43
pubmed: 23461720
Prostaglandins Leukot Essent Fatty Acids. 2021 Jan;164:102215
pubmed: 33276284
Science. 2016 Jul 8;353(6295):aad9969
pubmed: 27198673
Circ Res. 2016 Oct 14;119(9):1030-1038
pubmed: 27531933
J Biol Chem. 2007 Feb 23;282(8):5106-10
pubmed: 17218321
Hum Mol Genet. 2009 Feb 1;18(3):482-96
pubmed: 18996917
Am J Physiol Cell Physiol. 2012 Dec 15;303(12):C1292-300
pubmed: 23076793
J Pathol. 2007 Oct;213(2):229-38
pubmed: 17668421
Nat Med. 2015 Jul;21(7):786-94
pubmed: 26053624
Methods Mol Biol. 2012;798:311-24
pubmed: 22130845
Trends Mol Med. 2016 Jun;22(6):479-496
pubmed: 27161598
Arch Pharm Res. 2012 Jan;35(1):3-7
pubmed: 22297737
Hum Mol Genet. 2011 Feb 15;20(4):790-805
pubmed: 21118895
J Intern Med. 2010 Jul;268(1):15-24
pubmed: 20497301
Nat Immunol. 2019 May;20(5):626-636
pubmed: 30936495
Stem Cells Int. 2019 Jul 14;2019:4761427
pubmed: 31396285
Proc Natl Acad Sci U S A. 1983 Aug;80(15):4856-60
pubmed: 6576361
Nat Immunol. 2008 Aug;9(8):873-9
pubmed: 18568027
Neuromuscul Disord. 1997 Mar;7(2):117-25
pubmed: 9131653
Cells. 2020 Jul 18;9(7):
pubmed: 32708412
Mol Brain. 2018 Feb 13;11(1):9
pubmed: 29439730
J Cell Biol. 2001 Oct 1;155(1):123-31
pubmed: 11581289
Front Immunol. 2019 Jul 09;10:1591
pubmed: 31354730
Curr Protoc Immunol. 2008 Nov;Chapter 14:Unit 14.2
pubmed: 19016446
Nat Med. 2015 Dec;21(12):1455-63
pubmed: 26569381
Cell. 2013 Dec 5;155(6):1282-95
pubmed: 24315098
Stem Cells Transl Med. 2019 Oct;8(10):992-998
pubmed: 31187940
Am J Physiol Cell Physiol. 2016 Apr 15;310(8):C663-72
pubmed: 26825123
J Clin Invest. 2017 Jun 1;127(6):2418-2432
pubmed: 28481224
Cell. 2007 Jun 1;129(5):999-1010
pubmed: 17540178
Nat Methods. 2012 Jul;9(7):671-5
pubmed: 22930834
Neuropharmacology. 2018 Sep 1;139:182-193
pubmed: 30009833
Methods Mol Biol. 2017;1560:179-188
pubmed: 28155153
FASEB J. 2011 Jul;25(7):2399-407
pubmed: 21478260
PLoS Genet. 2019 Oct 18;15(10):e1008408
pubmed: 31626629
Nat Commun. 2019 Sep 2;10(1):3945
pubmed: 31477726
Neuroscience. 2009 May 19;160(3):651-60
pubmed: 19272428
J Exp Med. 2007 May 14;204(5):1057-69
pubmed: 17485518
J Cardiovasc Pharmacol. 2017 Jan;69(1):23-33
pubmed: 27676325