(ER) stress and components of the ER protein quality control in cardiac pathology is only just emerging. We recently proposed that activation of ER stress coping responses, including UPR, leading to the successful recovery of homeostasis at the cellular level could lead to pathological outcomes at the organismal level.
This study supports this notion, showing that transient activation of IRE1α in the heart led to permanent modification of the cellular program in the organ, culminating in cardiac fibrosis. Although activation of UPR may have promoted cardiomyocyte survival, the permanent activation of TGFβ1 pathways led to cardiac pathology and heart failure.
The silencing IRE1α activity by TUDCA specifically prevented the activation of the TGFβ1 pathways in vivo thereby preventing the ensuing fibrillogenesis.
The study was funded by the Canadian Institutes of Health Research.
Groenendyk J, Lee D, Jung J, Dyck JRB, Lopaschuk GD, Agellon LB, et al. (2016)
Inhibition of the Unfolded Protein Response Mechanism Prevents Cardiac Fibrosis
PLoS ONE 11(7): e0159682. doi:10.1371/journal.pone.0159682
Image: Anssi Koskinen/Flickr
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