Validation of highly selective sphingosine kinase 2 inhibitors SLM6031434 and HWG-35D as effective anti-fibrotic treatment options in a mouse model of tubulointerstitial fibrosis.
CTGF
Collagen I
HWG-35D
SK2 inhibition
SLM6031434
Smad7
Journal
Cellular signalling
ISSN: 1873-3913
Titre abrégé: Cell Signal
Pays: England
ID NLM: 8904683
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
28
09
2020
revised:
04
12
2020
accepted:
06
12
2020
pubmed:
11
12
2020
medline:
20
1
2022
entrez:
10
12
2020
Statut:
ppublish
Résumé
Renal fibrosis is characterized by chronic inflammation and excessive accumulation of extracellular matrix and progressively leads to functional insufficiency and even total loss of kidney function. In this study we investigated the anti-fibrotic potential of two highly selective and potent SK2 inhibitors, SLM6031434 and HWG-35D, in unilateral ureter obstruction (UUO), a model for progressive renal fibrosis, in mice. In both cases, treatment with SLM6031434 or HWG-35D resulted in an attenuated fibrotic response to UUO in comparison to vehicle-treated mice as demonstrated by reduced collagen accumulation and a decreased expression of collagen-1 (Col1), fibronectin-1 (FN-1), connective tissue growth factor (CTGF), and α-smooth muscle actin (α-SMA). Similar to our previous study in Sphk2
Identifiants
pubmed: 33301900
pii: S0898-6568(20)30358-2
doi: 10.1016/j.cellsig.2020.109881
pii:
doi:
Substances chimiques
Enzyme Inhibitors
0
Phosphotransferases (Alcohol Group Acceptor)
EC 2.7.1.-
sphingosine kinase 2, mouse
EC 2.7.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Validation Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
109881Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.