Journal
AUTOPHAGY
Volume 8, Issue 5, Pages 849-850Publisher
LANDES BIOSCIENCE
DOI: 10.4161/auto.19947
Keywords
liver fibrosis; autophagy; hepatic stellate cells; lipid droplets; chloroquine; Atg7
Categories
Funding
- NIAAA NIH HHS [R01 AA020709] Funding Source: Medline
- NIDDK NIH HHS [R01 DK056621] Funding Source: Medline
Ask authors/readers for more resources
Activation of hepatic stellate cells (HSC), a resident pericytic cell in liver, into a proliferative and fibrogenic cell type, is the principal event underlying hepatic fibrosis following injury. Release of lipid droplets (LD) containing retinyl esters and triglyceride is a defining feature of HSC activation, yet the basis for this release has remained mysterious. Here we offer a surprising discovery that autophagy is the missing link underlying LD release, by stimulating metabolism of their contents to provide the energy vital to fuel HSC activation. By specifically inhibiting the autophagic pathway in activated HSC, LD release is impaired and cellular ATP levels are decreased. Moreover, animals with HSC-specific deletion of Atg7 display attenuated activation following liver injury, leading to reduced fibrosis in vivo. We further demonstrate that fibrogenic cells from other organs, including kidney and lung, also rely on autophagy as a core pathway driving the scarring response. Our results provide a novel framework for understanding pathways underlying fibrogenic cell responses to tissue injury.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available