Progranulin attenuates liver fibrosis by downregulating the inflammatory response

Cited 36 time in scopus
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Title
Progranulin attenuates liver fibrosis by downregulating the inflammatory response
Author(s)
Wonbeak Yoo; Jaemin Lee; Kyung Hee Noh; S Lee; Dana Jung; M H Kabir; Dongmin Park; C Lee; Ki-Sun KwonJi-Su Kim; S Kim
Bibliographic Citation
Cell Death & Disease, vol. 10, no. 10, pp. 758-758
Publication Year
2019
Abstract
Progranulin (PGRN) is a cysteine-rich secreted protein expressed in endothelial cells, immune cells, neurons, and adipocytes. It was first identified for its growth factor-like properties, being implicated in tissue remodeling, development, inflammation, and protein homeostasis. However, these findings are controversial, and the role of PGRN in liver disease remains unknown. In the current study, we examined the effect of PGRN in two different models of chronic liver disease, methionine-choline-deficient diet (MCD)-induced non-alcoholic steatohepatitis (NASH) and carbon tetrachloride (CCl4)-induced liver fibrosis. To induce long-term expression of PGRN, PGRN-expressing adenovirus was delivered via injection into the tibialis anterior. In the CCl4-induced fibrosis model, PGRN showed protective effects against hepatic injury, inflammation, and fibrosis via inhibition of nuclear transcription factor kappa B (NF-κB) phosphorylation. PGRN also decreased lipid accumulation and inhibited pro-inflammatory cytokine production and fibrosis in the MCD-induced NASH model. In vitro treatment of primary macrophages and Raw 264.7 cells with conditioned media from hepatocytes pre-treated with PGRN prior to stimulation with tumor necrosis factor (TNF)-α or palmitate decreased their expression of pro-inflammatory genes. Furthermore, PGRN suppressed inflammatory and fibrotic gene expression in a cell culture model of hepatocyte injury and primary stellate cell activation. These observations increase our understanding of the role of PGRN in liver injury and suggest PGRN delivery as a potential therapeutic strategy in chronic inflammatory liver disease.
ISSN
2041-4889
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/s41419-019-1994-2
Type
Article
Appears in Collections:
Division of Research on National Challenges > Bionanotechnology Research Center > 1. Journal Articles
Aging Convergence Research Center > 1. Journal Articles
Jeonbuk Branch Institute > Primate Resources Center > 1. Journal Articles
Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
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