Involvement of eIF2α in halofuginone-driven inhibition of TGF-ß1-induced EMT.
J Biosci
; 452020.
Article
en En
| MEDLINE
| ID: mdl-32457283
Halofuginone (HF) is an extract from the widely used traditional Chinese medicine (TCM) Dichroa febrifuga that facilitates the recovery of wounds and attenuates hepatic fibrosis. However, the role of HF in the epithelial-mesenchymal transition (EMT) of IPEC-J2 cells remains unclear. The current study explored the anti-EMT effect of HF in IPEC-J2 cells and illustrates its molecular mechanism. Transforming growth factor ß1 (TGF-ß1), as a recognized profibrogenic cytokine, decreased the level of the epithelial marker E-cadherin and increased the level of the mesenchymal markers, such as N-cadherin, fibronectin (FN), vimentin (Vim), and α-smooth muscle actin (α-SMA), in IPEC-J2 cells depending on the exposure time and dose. HF markedly prevented the EMT induced by TGF-ß1. Dissection of the mechanism revealed that HF inhibited IPEC-J2 cell EMT via modulating the phosphorylation of SMAD2/3 and the SMAD2/3-SMAD4 complex nuclear translocation. Furthermore, HF could promote the phosphorylation of eukaryotic translation initiation factor-2α (eIF2α), which modulates the SMAD signaling pathway. These results suggested that HF inhibits TGF-ß1-induced EMT in IPEC-J2 cells through the eIF2α/SMAD signaling pathway. Our findings suggest that HF can serve as a potential anti-EMT agent in intestinal fibrosis therapy.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Piperidinas
/
Factor 2 Eucariótico de Iniciación
/
Enterocitos
/
Quinazolinonas
/
Factor de Crecimiento Transformador beta1
/
Transición Epitelial-Mesenquimal
/
Antineoplásicos
Límite:
Animals
Idioma:
En
Revista:
J Biosci
Año:
2020
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
India