Progranulin attenuates liver fibrosis by downregulating the inflammatory response

Cited 17 time in scopus
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dc.contributor.authorWonbeak Yoo-
dc.contributor.authorJaemin Lee-
dc.contributor.authorKyung Hee Noh-
dc.contributor.authorS Lee-
dc.contributor.authorDana Jung-
dc.contributor.authorM H Kabir-
dc.contributor.authorDongmin Park-
dc.contributor.authorC Lee-
dc.contributor.authorKi-Sun Kwon-
dc.contributor.authorJi-Su Kim-
dc.contributor.authorS Kim-
dc.date.accessioned2019-10-28T16:30:45Z-
dc.date.available2019-10-28T16:30:45Z-
dc.date.issued2019-
dc.identifier.issn20414889-
dc.identifier.uri10.1038/s41419-019-1994-2ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/19023-
dc.description.abstractProgranulin (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.-
dc.publisherSpringer-Nature Pub Group-
dc.titleProgranulin attenuates liver fibrosis by downregulating the inflammatory response-
dc.title.alternativeProgranulin attenuates liver fibrosis by downregulating the inflammatory response-
dc.typeArticle-
dc.citation.titleCell Death & Disease-
dc.citation.number10-
dc.citation.endPage758-
dc.citation.startPage758-
dc.citation.volume10-
dc.contributor.affiliatedAuthorWonbeak Yoo-
dc.contributor.affiliatedAuthorJaemin Lee-
dc.contributor.affiliatedAuthorKyung Hee Noh-
dc.contributor.affiliatedAuthorDana Jung-
dc.contributor.affiliatedAuthorDongmin Park-
dc.contributor.affiliatedAuthorKi-Sun Kwon-
dc.contributor.affiliatedAuthorJi-Su Kim-
dc.contributor.alternativeName유원백-
dc.contributor.alternativeName이재민-
dc.contributor.alternativeName노경희-
dc.contributor.alternativeName이상민-
dc.contributor.alternativeName정다나-
dc.contributor.alternativeNameKabir-
dc.contributor.alternativeName박동민-
dc.contributor.alternativeName이철주-
dc.contributor.alternativeName권기선-
dc.contributor.alternativeName김지수-
dc.contributor.alternativeName김석호-
dc.identifier.bibliographicCitationCell Death & Disease, vol. 10, no. 10, pp. 758-758-
dc.identifier.doi10.1038/s41419-019-1994-2-
dc.description.journalClassY-
Appears in Collections:
Division of Research on National Challenges > Stem Cell Convergenece Research Center > 1. Journal Articles
Jeonbuk Branch Institute > Primate Resources Center > 1. Journal Articles
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