Adrenomedullin regulates expressions of transforming growth factor-β1 and β1-induced matrix metalloproteinase-2 in hepatic stellate cells

Adrenomedullin (AM), a peptide isolated from human pheochromocytoma, can be produced and secreted by various types of cells including hepatic stellate cells (HSCs), and its possible role in HSCs is not clear now. In the present study, the interactive regulation between transforming growth factor (TGF)-beta 1 and AM and the effect of AM on TGF-beta 1-induced matrix metalloproteinase (MMP)-2 expression in HSCs were investigated. TGF-beta 1 and AM inhibited gene transcript level mutually (real-time reverse transcription-polymerase chain reaction). AM suppressed the protein expression level of TGF-beta 1 (Western blot), but TGF-beta 1 might have no effect on AM secretion level. MMP-2 protein expression in HSCs was increased in response to TGF-beta 1, and upregulation of MMP-2 expression stimulated with TGF-beta 1 was suppressed by AM in dose-dependent manner (Western blot). AM decreased the phosphorylation level of extracellular signal-regulated kinase (ERK) in HSCs treated with TGF-beta 1, and TGF-beta 1-induced MMP-2 expression was suppressed by adding Mitogen-activated protein Kinase/ERK (MEK) inhibitor U-0126 (Western blot). Our results suggest that AM may intervene the activation of HSCs by inhibiting TGF-beta 1 production and TGF-beta 1-induced MMP-2 expression; AM may suppress the upregulation. of MMP-2 expression induced by TGF-beta 1 partially through ERK pathway.