Adrenergic stimulation of hepatocyte growth factor expression

Hepatocyte growth factor (HGF), a potent mitogen, is released into plasma a t increased levels following injury to certain tissues, including the liver . Early increases in plasma HGF are not due to a release from the injured l iver, but rather from distal organs, particularly the lung. We have investi gated the ability of norepinephrine (NE), which rises rapidly in plasma aft er liver resection, to trigger elevated production of HGF in MRC-5 human em bryonic lung fibroblasts. Levels of HGF released to culture media and of HG F mRNA increased when cultures were exposed to NE, or to other adrenergic a gonists, While stimulation of either beta- or alpha(1)-adrenergic receptors increased HGF expression, responses to NE appear to be mediated primarily via beta receptors, Since NE has already been shown to act as a comitogen w ith HGF, our findings suggest that adrenergic hormones may act both to indu ce production of HGF at distal sites, and to enhance the response to HGF at target tissues. (C) 1999 Academic Press.