Ruxolitinib Alleviates Renal Interstitial Fibrosis in UUO Mice.
Animals
Apoptosis
/ drug effects
Blotting, Western
Cell Line
Chemokine CCL2
Epithelial Cells
Epithelial-Mesenchymal Transition
Fibroblasts
/ drug effects
Fibrosis
Immunohistochemistry
In Situ Nick-End Labeling
Janus Kinase 1
Janus Kinase 2
Kidney Diseases
/ drug therapy
Male
Mice
Mice, Inbred C57BL
Nitriles
Oxidative Stress
/ drug effects
Pyrazoles
/ therapeutic use
Pyrimidines
RNA, Messenger
/ metabolism
Rats
Real-Time Polymerase Chain Reaction
STAT3 Transcription Factor
Signal Transduction
/ drug effects
Transforming Growth Factor beta1
/ metabolism
Ureteral Obstruction
/ drug therapy
Jak
Ruxolitinib
Stat3
TGF-β1
mTOR
Journal
International journal of biological sciences
ISSN: 1449-2288
Titre abrégé: Int J Biol Sci
Pays: Australia
ID NLM: 101235568
Informations de publication
Date de publication:
2020
2020
Historique:
received:
09
08
2019
accepted:
15
10
2019
entrez:
14
1
2020
pubmed:
14
1
2020
medline:
3
11
2020
Statut:
epublish
Résumé
Ruxolitinib is a selective inhibitor of Jak1/2. Downstream signaling pathways of Jak, such as Stat3 and Akt/mTOR, are overactivated and contribute to renal interstitial fibrosis. Therefore, we explored the effect of Ruxolitinib on this pathological process. Unilateral ureteral obstruction (UUO) models and TGF-β1-treated fibroblasts and renal tubular epithelial cells were adopted in this study. Ruxolitinib was administered to UUO mice and TGF-β1-treated cells. Kidneys from UUO mice with Ruxolitinib treatment displayed less tubular injuries compared with those without Ruxolitinib treatment. Ruxolitinib treatment suppressed fibroblast activation and extracellular matrix (ECM) production in UUO kidneys and TGF-β1-treated fibroblasts. Ruxolitinib treatment also blocked epithelial-mesenchymal transition (EMT) in UUO kidneys and TGF-β 1-treated renal tubular epithelial cells. Moreover, Ruxolitinib treatment alleviated UUO-induced inflammation, oxidative stress and apoptosis. Mechanistically, Ruxolitinib treatment attenuated activation of both Stat3 and Akt/mTOR/Yap pathways. In conclusion, Ruxolitinib treatment can ameliorate UUO-induced renal interstitial fibrosis, suggesting that Ruxolitinib may be potentially used to treat fibrotic kidney disease.
Identifiants
pubmed: 31929748
doi: 10.7150/ijbs.39024
pii: ijbsv16p0194
pmc: PMC6949153
doi:
Substances chimiques
Chemokine CCL2
0
Nitriles
0
Pyrazoles
0
Pyrimidines
0
RNA, Messenger
0
STAT3 Transcription Factor
0
Transforming Growth Factor beta1
0
ruxolitinib
82S8X8XX8H
Janus Kinase 1
EC 2.7.10.2
Janus Kinase 2
EC 2.7.10.2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
194-203Informations de copyright
© The author(s).
Déclaration de conflit d'intérêts
Competing Interests: The authors have declared that no competing interest exists.
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