Species-specific control of hepatocyte growth factor expression and production in adipocytes in a differentiation-dependent manner

Abstract

Hepatocyte growth factor (HGF) is a mesenchymal cell-derived factor that regulates cell growth, cell motility, and morphogenesis. Since there are conflicting reports on HGF-producing cells, we herein examined HGF activity in conditioned medium (CM) of bovine and mouse preadipocytes before and after adipogenic differentiation. CM of bovine adipocytes and mouse preadipocytes induced the morphogenesis of mammary epithelial cells that was inhibited by an NK4 HGF antagonist, whereas CM of bovine preadipocytes and mouse adipocytes did not. HGF mRNA expression was increased by a treatment with dexamethasone and isobutylmethylxanthine in bovine as well as human cells, whereas it was decreased in rodent cells. It was unfortunate that HGF gene promoter activity failed to reflect HGF mRNA expression in these cells. After actinomycin D treatment, expression of HGF mRNA remained stable in pre- and differentiated bovine adipocytes and mouse preadipocytes, whereas rapidly decreased in mouse-differentiated adipocytes. These results indicate that expression and production of HGF are regulated in a species-specific adipogenic differentiation-dependent manner and suggest that the decrease in HGF mRNA in mouse differentiated adipocytes is, at least in part, mediated by differentiation-dependent loss of its stability.