The role of Nrf2 in acute and chronic muscle injury

2020
journal article
article
dc.abstract.enThe nuclear factor erythroid 2-related factor 2 (Nrf2) is considered as a master cytoprotective factor regulating the expression of genes encoding anti-oxidant, anti-inflammatory, and detoxifying proteins. The role of Nrf2 in the pathophysiology of skeletal muscles has been evaluated in different experimental models, however, due to inconsistent data, we aimed to investigate how Nrf2 transcriptional deficiency (Nrf2(tKO)) affects muscle functions both in an acute and chronic injury. The acute muscle damage was induced in mice of two genotypes-WT and Nrf2(tKO) mice by cardiotoxin (CTX) injection. To investigate the role of Nrf2 in chronic muscle pathology, mdx mice that share genetic, biochemical, and histopathological features with Duchenne muscular dystrophy (DMD) were crossed with mice lacking transcriptionally active Nrf2 and double knockouts (mdx/Nrf2(tKO)) were generated. To worsen the dystrophic phenotype, the analysis of disease pathology was also performed in aggravated conditions, by applying a long-term treadmill test. We have observed slightly increased muscle damage in Nrf2(tKO) mice after CTX injection. Nevertheless, transcriptional ablation of Nrf2 in mdx mice did not significantly aggravate the most deleterious, pathological hallmarks of DMD related to degeneration, inflammation, fibrotic scar formation, angiogenesis, and the number and proliferation of satellite cells in non-exercised conditions. On the other hand, upon chronic exercises, the degeneration and inflammatory infiltration of the gastrocnemius muscle, but not the diaphragm, turned to be increased in Nrf2(tKO)mdx in comparison to mdx mice. In conclusion, the lack of transcriptionally active Nrf2 influences moderately muscle pathology in acute CTX-induced muscle injury and chronic DMD mouse model, without affecting muscle functionality. Hence, in general, we demonstrated that the deficiency of Nrf2 transcriptional activity has no profound impact on muscle pathology in various models of muscle injury.pl
dc.affiliationWydział Biochemii, Biofizyki i Biotechnologii : Zakład Biotechnologii Medycznejpl
dc.affiliationPion Prorektora ds. badań naukowych : Małopolskie Centrum Biotechnologiipl
dc.contributor.authorBronisz-Budzyńska, Iwona - 253420 pl
dc.contributor.authorKozakowska, Magdalena - 135802 pl
dc.contributor.authorPodkalicka, Paulina - 201153 pl
dc.contributor.authorKachamakova-Trojanowska, Neli - 160104 pl
dc.contributor.authorŁoboda, Agnieszka - 130081 pl
dc.contributor.authorDulak, Józef - 127818 pl
dc.date.accessioned2021-04-26T11:19:39Z
dc.date.available2021-04-26T11:19:39Z
dc.date.issued2020pl
dc.date.openaccess0
dc.description.accesstimew momencie opublikowania
dc.description.versionostateczna wersja wydawcy
dc.description.volume10pl
dc.identifier.articleid35pl
dc.identifier.doi10.1186/s13395-020-00255-0pl
dc.identifier.eissn2044-5040pl
dc.identifier.projectROD UJ / OPpl
dc.identifier.urihttps://ruj.uj.edu.pl/xmlui/handle/item/269788
dc.languageengpl
dc.language.containerengpl
dc.rightsUdzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa*
dc.rights.licenceCC-BY
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/legalcode.pl*
dc.share.typeotwarte czasopismo
dc.subject.encardiotoxin-induced injurypl
dc.subject.enDuchenne muscular dystrophypl
dc.subject.eninflammationpl
dc.subject.enNrf2pl
dc.subject.enregenerationpl
dc.subject.ensatellite cellspl
dc.subject.enskeletal musclepl
dc.subject.enmdxpl
dc.subtypeArticlepl
dc.titleThe role of Nrf2 in acute and chronic muscle injurypl
dc.title.journalSkeletal Musclepl
dc.typeJournalArticlepl
dspace.entity.typePublication
dc.abstract.enpl
The nuclear factor erythroid 2-related factor 2 (Nrf2) is considered as a master cytoprotective factor regulating the expression of genes encoding anti-oxidant, anti-inflammatory, and detoxifying proteins. The role of Nrf2 in the pathophysiology of skeletal muscles has been evaluated in different experimental models, however, due to inconsistent data, we aimed to investigate how Nrf2 transcriptional deficiency (Nrf2(tKO)) affects muscle functions both in an acute and chronic injury. The acute muscle damage was induced in mice of two genotypes-WT and Nrf2(tKO) mice by cardiotoxin (CTX) injection. To investigate the role of Nrf2 in chronic muscle pathology, mdx mice that share genetic, biochemical, and histopathological features with Duchenne muscular dystrophy (DMD) were crossed with mice lacking transcriptionally active Nrf2 and double knockouts (mdx/Nrf2(tKO)) were generated. To worsen the dystrophic phenotype, the analysis of disease pathology was also performed in aggravated conditions, by applying a long-term treadmill test. We have observed slightly increased muscle damage in Nrf2(tKO) mice after CTX injection. Nevertheless, transcriptional ablation of Nrf2 in mdx mice did not significantly aggravate the most deleterious, pathological hallmarks of DMD related to degeneration, inflammation, fibrotic scar formation, angiogenesis, and the number and proliferation of satellite cells in non-exercised conditions. On the other hand, upon chronic exercises, the degeneration and inflammatory infiltration of the gastrocnemius muscle, but not the diaphragm, turned to be increased in Nrf2(tKO)mdx in comparison to mdx mice. In conclusion, the lack of transcriptionally active Nrf2 influences moderately muscle pathology in acute CTX-induced muscle injury and chronic DMD mouse model, without affecting muscle functionality. Hence, in general, we demonstrated that the deficiency of Nrf2 transcriptional activity has no profound impact on muscle pathology in various models of muscle injury.
dc.affiliationpl
Wydział Biochemii, Biofizyki i Biotechnologii : Zakład Biotechnologii Medycznej
dc.affiliationpl
Pion Prorektora ds. badań naukowych : Małopolskie Centrum Biotechnologii
dc.contributor.authorpl
Bronisz-Budzyńska, Iwona - 253420
dc.contributor.authorpl
Kozakowska, Magdalena - 135802
dc.contributor.authorpl
Podkalicka, Paulina - 201153
dc.contributor.authorpl
Kachamakova-Trojanowska, Neli - 160104
dc.contributor.authorpl
Łoboda, Agnieszka - 130081
dc.contributor.authorpl
Dulak, Józef - 127818
dc.date.accessioned
2021-04-26T11:19:39Z
dc.date.available
2021-04-26T11:19:39Z
dc.date.issuedpl
2020
dc.date.openaccess
0
dc.description.accesstime
w momencie opublikowania
dc.description.version
ostateczna wersja wydawcy
dc.description.volumepl
10
dc.identifier.articleidpl
35
dc.identifier.doipl
10.1186/s13395-020-00255-0
dc.identifier.eissnpl
2044-5040
dc.identifier.projectpl
ROD UJ / OP
dc.identifier.uri
https://ruj.uj.edu.pl/xmlui/handle/item/269788
dc.languagepl
eng
dc.language.containerpl
eng
dc.rights*
Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa
dc.rights.licence
CC-BY
dc.rights.uri*
http://creativecommons.org/licenses/by/4.0/legalcode.pl
dc.share.type
otwarte czasopismo
dc.subject.enpl
cardiotoxin-induced injury
dc.subject.enpl
Duchenne muscular dystrophy
dc.subject.enpl
inflammation
dc.subject.enpl
Nrf2
dc.subject.enpl
regeneration
dc.subject.enpl
satellite cells
dc.subject.enpl
skeletal muscle
dc.subject.enpl
mdx
dc.subtypepl
Article
dc.titlepl
The role of Nrf2 in acute and chronic muscle injury
dc.title.journalpl
Skeletal Muscle
dc.typepl
JournalArticle
dspace.entity.type
Publication

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