Farnesoid X receptor activation inhibits TGFBR1/TAK1-mediated vascular inflammation and calcification via miR-135a-5p.
Animals
Aorta
/ cytology
Calcinosis
/ genetics
Cells, Cultured
Female
Humans
MAP Kinase Kinase Kinases
/ genetics
Male
MicroRNAs
/ genetics
Muscle, Smooth, Vascular
/ cytology
Osteogenesis
Rats, Wistar
Receptor, Transforming Growth Factor-beta Type I
/ genetics
Receptors, Cytoplasmic and Nuclear
/ genetics
Renal Insufficiency, Chronic
/ etiology
Vasculitis
/ genetics
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
24 06 2020
24 06 2020
Historique:
received:
22
10
2019
accepted:
08
06
2020
entrez:
26
6
2020
pubmed:
26
6
2020
medline:
24
6
2021
Statut:
epublish
Résumé
Chronic inflammation plays a crucial role in vascular calcification. However, only a few studies have revealed the mechanisms underlying the development of inflammation under high-phosphate conditions in chronic kidney disease (CKD) patients. Here, we show that inflammation resulting from the activation of the TGFBR1/TAK1 pathway is involved in calcification in CKD rats or osteogenic medium-cultured human aortic smooth muscle cells (HASMCs). Moreover, miR-135a-5p is demonstrated to be a key regulator of the TGFBR1/TAK1 pathway, which has been reported to be decreased in CKD rats. We further reveal that farnesoid X receptor (FXR) activation increases miR-135a-5p expression, thereby inhibiting the activation of the TGFBR1/TAK1 pathway, ultimately resulting in the attenuation of vascular inflammation and calcification in CKD rats. Our findings provide advanced insights into the mechanisms underlying the development of inflammation in vascular calcification, and evidence that FXR activation could serve as a therapeutic strategy for retarding vascular calcification in CKD patients.
Identifiants
pubmed: 32581266
doi: 10.1038/s42003-020-1058-2
pii: 10.1038/s42003-020-1058-2
pmc: PMC7314757
doi:
Substances chimiques
MIRN135 microRNA, human
0
MicroRNAs
0
Receptors, Cytoplasmic and Nuclear
0
farnesoid X-activated receptor
0C5V0MRU6P
MAP Kinase Kinase Kinases
EC 2.7.11.25
MAP kinase kinase kinase 7
EC 2.7.11.25
Receptor, Transforming Growth Factor-beta Type I
EC 2.7.11.30
TGFBR1 protein, human
EC 2.7.11.30
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
327Commentaires et corrections
Type : ErratumIn
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