Osteoprotegerin Is more than a Possible Serum Marker in Liver Fibrosis: A Study into Its Function in Human and Murine Liver
Penulis/Author
Dr. Adhyatmika, M.Biotech., Apt. (1); Leonie Beljaars (2); Kurnia S. S. Putri (3); Habibie (4); Carian E. Boorsma (5); Catharina Reker-Smit (6); Theerut Luangmonkong (7); Burak Guney (8); Axel Haak (9); Keri A. Mangnus (10); Eduard Post (11); Klaas Poelstra (12); Kim Ravnskjaer (13); Peter Olinga (14); Barbro N. Melgert (15)
Tanggal/Date
21 2020
Kata Kunci/Keyword
Abstrak/Abstract
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 ?1 (TGF?1) stimulation. Moreover, OPG itself stimulated expression of genes associated with fibrogenesis in liver slices through TGF?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?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.
