Enhanced expression of bone morphogenetic protein endothelial cell-precursor derived regulator in liver fibrosis

There are conflicting data on the role of different bone morphogenic proteins (BMPs) in hepatic fibrosis; some have been shown to act act profibrogenic such as BMP4 and others rather anti-fibrogenic such as BMP6. BMP endothelial cell-precursor derived regulator (BMPER) has been shown to act as extracellular regulator of different BMP-proteins including BMP4 and BMP6. Depending on its concentration and the cellular environment, BMPER has been shown to be able to enhance but also to attenuate BMP signalling.

The aim of this study was to investigate the expression and role of BMPER in hepatic fibrosis.

Methods and results BMPER mRNA- and protein-expression is significantly increased during in vitro activation of primary human hepatic stellate cells (HSC). Furthermore, hepatic BMPER-expression is significantly increased in different mouse models of liver-fibrosis. Moreover, there is a significant correlation between the expression of BMPER and alpha-smooth muscle actin (alpha-sma) in human liver tissues and immunofluorescence analysis revealed co-localization of BMPER and alpha-sma expression in human cirrhosis.

In activated HSC, BMPER-depletion with siRNA caused a downregulation of the expression of inhibitor of differentiation 1 (ID1), a well-characterized read-out for BMP-pathway-activity. Conversely, stimulation with recombinant BMPER induced ID1-expression in activated HSCs.

Summary and conclusion Activated HSC are the cellular source of enhanced BMPER expression in hepatic fibrosis and in vitro studies indicate that BMPER causes an upregulation of BMP-activity in HSC. Further studies are required to analyse the interaction of BMPER with different BMPs and its role during the course of hepatic fibrosis.

Publication History

Article published online:
26 January 2022