Role of BMP-9 in human liver disease

Abstract

We read with interest the article by Breitkopf-Heinlein et al ,1 investigating the role of bone morphogenetic protein (BMP)-9 in liver regeneration and fibrosis. In mice, the authors demonstrate that BMP-9, a member of the transforming growth factor-β family, is primarily produced by hepatic stellate cells (HSCs) and is a profibrogenic factor. Inhibition or knockout of BMP-9 reduced liver fibrosis, while the recombinant protein increased the proliferation and migration of human HSCs. However, as shown in figure 1H and I of that study, rhBMP-9 did not upregulate fibrosis markers (eg, collagen I, fibronectin, platelet-derived growth factor B and α smooth muscle actin). While BMP-9 expression increased during the activation of primary human HSCs, the authors were unable to demonstrate a correlation between human hepatic BMP-9 expression and liver fibrosis stage from a publicly available microarray dataset. Figure 1 mRNA expression of BMP-9 pathway genes in human liver disease from microarray data. Boxplots showing BMP-9, BMP-10, Alk1 and ACVR2B mRNA in liver from normal and cirrhosis subjects (A), obese subjects with healthy liver and patients with NASH (B), and patients with mild …