Phorbol ester‐induced secretion of human hepatocyte growth factor by human skin fibroblasts and its inhibition by dexamethasone

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Abstract
Human skin fibroblasts secreted a certain amount of human hepatocyte growth factor (hHGF), as determined by an enzyme‐linked immunosorbent assay for hHGF. This hHGF secretion was remarkably stimulated by protein kinase C (PKC)‐activating phorbol esters, which was inhibited by the simultaneous addition of dexamethasone. Pretreatment with phorbol 12‐myristate 13‐acetate (PMA) caused a down‐regulation in hHGF secretion. hHGF secreted by the PMA‐treated cells showed a potent hepatocyle growth‐promoting activity which was neutralized by an anti‐hHGF antiserum. These results indicate both that PMA‐treated human skin fibroblasts produce biologically active hHGF and the possible involvement of PKC activation in this process.