Lipoxin A4 inhibited the activation of hepatic stellate cells -T6 cells by modulating profibrotic cytokines and NF-κB signaling pathway.
Prostaglandins Other Lipid Mediat
; 146: 106380, 2020 02.
Article
en En
| MEDLINE
| ID: mdl-31698141
ABSTRACT
BACKGROUND:
The deposition of extracellular matrix (ECM) during hepatic fibrosis is an intermediate process in the progression of multiple chronic liver diseases to cirrhosis. Because activated hepatic stellate cells (HSCs) are the main source of ECM, HSCs activation is the central link in the formation of liver fibrosis. It was reported that the analogs of lipoxin A4 (LXA4) had anti-fibrotic effects, but the mechanisms are still not clear. This study was conducted to explore the possible mechanisms involved in the process of LXA4-mediated inhibition of HSCs activation.METHODS:
Rat HSC-T6 cells were activated by LPS and treated with LXA4 and/or BOC-2. The levels of ECM were assessed by hydroxyproline (Hyp) kit. The protein levels of α-SMA, Collagen I and III, MMP-2, MMP-9, TGF-ß1, PDGF A and B, NF-κB P65, phosphorylated NF-κB P65 (P-P65) and NF-κB inhibitor α (I-κBα) were measured via western blot. The mRNA levels of MMP-2 and MMP-9 were observed by real-time PCR. The contents of TGF-ß1 and PDGF were assessed by ELISA kits. Nuclear transfer assay kit was used to assess the activation and translation of NF-κB P65.RESULTS:
(1) LPS activated HSC-T6 cells and up-regulated α-SMA, but LXA4 decreased LPS-induced α-SMA in HSC-T6 cells. (2) LXA4 inhibited LPS-induced Hyp production, meanwhile down-regulated LPS-induced Collagen I, Collagen III, MMP-2, and MMP-9 in HSC-T6 cells. (3) LXA4 decreased LPS-induced TGF-ß1 and PDGF in HSC-T6 cells. (4) LXA4 repressed LPS-activated NF-κB signaling pathway, causing a reduction of I-κBα degradation, NF-κB phosphorylation, and NF-κB p65 transposition in HSC-T6 cells. (4) BOC-2, the blocker of LXA4 receptor, inhibited all the effects of LXA4.CONCLUSION:
LXA4 inhibited HSCs activation through down-regulation TGF-ß1/PDGF, and repression NF-κB signal pathway.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Citocinas
/
Lipoxinas
/
Factor de Transcripción ReIA
/
Células Estrelladas Hepáticas
Límite:
Humans
Idioma:
En
Revista:
Prostaglandins Other Lipid Mediat
Asunto de la revista:
ENDOCRINOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
China