Osteoprotegerin Is more than a Possible Serum Marker in Liver Fibrosis: A Study into Its Function in Human and Murine Liver

被引：19

作者：

Adhyatmika, Adhyatmika ^{[1
,2
]}

Beljaars, Leonie ^{[3
]}

Putri, Kurnia S. S. ^{[3
,4
]}

Habibie, Habibie ^{[5
,6
,7
]}

Boorsma, Carian E. ^{[1
]}

Reker-Smit, Catharina ^{[1
]}

Luangmonkong, Theerut ^{[3
,8
]}

Guney, Burak ^{[1
]}

Haak, Axel ^{[1
]}

Mangnus, Keri A. ^{[1
]}

Post, Eduard ^{[1
]}

Poelstra, Klaas ^{[1
]}

Ravnskjaer, Kim ^{[9
]}

Olinga, Peter ^{[3
]}

Melgert, Barbro N. ^{[5
,7
]}

机构：

[1] Univ Groningen, Groningen Res Inst Pharm, Dept Pharmacokinet Toxicol & Targeting, NL-9713 AV Groningen, Netherlands

[2] Gadjah Mada Univ, Fac Pharm, Dept Pharmaceut, Yogyakarta 55281, Indonesia

[3] Univ Groningen, Groningen Res Inst Pharm, Dept Pharmaceut Technol & Biopharm, NL-9713 AV Groningen, Netherlands

[4] Univ Indonesia, Fac Pharm, Depok 16424, Indonesia

[5] Univ Groningen, Groningen Res Inst Pharm, Dept Mol Pharmacol, NL-9713 AV Groningen, Netherlands

[6] Hasanuddin Univ, Fac Pharm, Makassar 90245, Indonesia

[7] Univ Med Ctr Groningen, Groningen Res Inst Asthma & COPD GRIAC, NL-9713 GZ Groningen, Netherlands

[8] Mahidol Univ, Fac Pharm, Bangkok 73170, Thailand

[9] Univ Southern Denmark, Dept Biochem & Mol Biol, DK-5230 Odense M, Denmark

来源：

PHARMACEUTICS | 2020年 / 12卷 / 05期

关键词：

cirrhosis; TGF beta 1; CCl4; resolution; hepatic stellate cells; osteoprotegerin; RANKL; TRAIL; PRECISION-CUT LIVER; RECEPTOR ACTIVATOR; RANKL; CELLS; FIBROGENESIS; EXPRESSION; APOPTOSIS; SLICES; LIGAND; VIVO;

D O I：

10.3390/pharmaceutics12050471

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Osteoprotegerin (OPG) serum levels are associated with liver fibrogenesis and have been proposed as a biomarker for diagnosis. However, the source and role of OPG in liver fibrosis are unknown, as is the question of whether OPG expression responds to treatment. Therefore, we aimed to elucidate the fibrotic regulation of OPG production and its possible function in human and mouse livers. OPG levels were significantly higher in lysates of human and mouse fibrotic livers compared to healthy livers. Hepatic OPG expression localized in cirrhotic collagenous bands in and around myofibroblasts. Single cell sequencing of murine liver cells showed hepatic stellate cells (HSC) to be the main producers of OPG in healthy livers. Using mouse precision-cut liver slices, we found OPG production induced by transforming growth factor beta 1 (TGF beta 1) stimulation. Moreover, OPG itself stimulated expression of genes associated with fibrogenesis in liver slices through TGF beta 1, suggesting profibrotic activity of OPG. Resolution of fibrosis in mice was associated with decreased production of OPG compared to ongoing fibrosis. OPG may stimulate fibrogenesis through TGF beta 1 and is associated with the degree of fibrogenesis. It should therefore be investigated further as a possible drug target for liver fibrosis or biomarker for treatment success of novel antifibrotics.

引用

页数：21

共 40 条

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