The ER Unfolded Protein Response Effector, ATF6, Reduces Cardiac Fibrosis and Decreases Activation of Cardiac Fibroblasts.
Int J Mol Sci
; 21(4)2020 Feb 18.
Article
in En
| MEDLINE
| ID: mdl-32085622
ABSTRACT
Activating transcription factor-6 α (ATF6) is one of the three main sensors and effectors of the endoplasmic reticulum (ER) stress response and, as such, it is critical for protecting the heart and other tissues from a variety of environmental insults and disease states. In the heart, ATF6 has been shown to protect cardiac myocytes. However, its roles in other cell types in the heart are unknown. Here we show that ATF6 decreases the activation of cardiac fibroblasts in response to the cytokine, transforming growth factor ß (TGFß), which can induce fibroblast trans-differentiation into a myofibroblast phenotype through signaling via the TGFß-Smad pathway. ATF6 activation suppressed fibroblast contraction and the induction of α smooth muscle actin (αSMA). Conversely, fibroblasts were hyperactivated when ATF6 was silenced or deleted. ATF6 thus represents a novel inhibitor of the TGFß-Smad axis of cardiac fibroblast activation.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Endoplasmic Reticulum
/
Activating Transcription Factor 6
/
Unfolded Protein Response
/
Fibroblasts
/
Myocardium
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Int J Mol Sci
Year:
2020
Type:
Article
Affiliation country:
United States