BONE MORPHOGENETIC PROTEIN-6 IS EXPRESSED IN NONPARENCHYMAL LIVER-CELLS AND UP-REGULATED BY TRANSFORMING GROWTH-FACTOR-BETA-1

Bone morphogenetic protein-6 (BMP-6) is a member of the TGF-beta super family, which controls growth and differentiation during embryogenesis and acts as an osteoinductive factor in the adult organism. In order to gain further insights into the role of BMP-6, the present study ana lyzed the expression pattern of BMP-6 in adult rat tissues with specia l emphasis to the liver, since TGF-beta 1, another member of the TGF-b eta superfamily, has been shown to play a fundamental role in liver ph ysiology. Rat BMP-6 coding cDNAs were generated by homology cloning us ing RT-PCR and displayed 89.6 and 83.4% homology to mouse and human BM P-6, respectively. By Northern blotting BMP-6-specific transcripts 3.7 kb in size were detected in major amounts in lung and in minor quanti ties in spleen, kidney, heart, brain, and liver. Among the different h epatic cell populations tested BMP-6 expression was confined to nonpar enchymal liver cells, namely rat hepatic stellate cells (HSC) and Kupf fer cells (KC). During primary culture BMP-6 expression was increased in HSC but declined in KC. Interestingly, TGF-beta 1 stimulated BMP-6 expression of HSC especially at an early time point of culture, while interferon-gamma downregulated BMP-6 expression. The detection of BMP- 6 transcripts in the liver, the cell-type-restricted expression patter n, and its regulation propose that, in addition to its osteoinductive properties, BMP-B might play a role in liver growth and differentiatio n, in particular after tissue damage. (C) 1997 Academic Press.