Hepatocyte growth factor signaling pathway inhibits cholesterol 7alpha-hydroxylase and bile acid synthesis in human hepatocytes.

Hepatocyte growth factor signaling pathway inhibits cholesterol 7alpha-hydroxylase and bile acid synthesis in human hepatocytes.

Song Kwang-Hoon; Ellis Ewa; Strom Stephen; Chiang John Y L

Hepatology (Baltimore, Md.)

2007

2007-12

UNLABELLED: Bile acid synthesis in the liver is regulated by the rate-limiting enzyme cholesterol 7alpha-hydroxylase (CYP7A1). Transcription of the CYP7A1 gene is inhibited by bile acids and cytokines. The rate of bile acid synthesis is reduced immediately after partial hepatectomy and during the early stage of liver regeneration. Hepatocyte growth factor (HGF) released from stellate cells activates a receptor tyrosine kinase c-Met, in hepatocytes and stimulates signaling pathways that regulate cell growth, proliferation, and apoptosis. This study demonstrated that HGF strongly and rapidly repressed CYP7A1 mRNA expression and the rate of bile acid synthesis in primary human hepatocytes. HGF rapidly induced c-Jun and small heterodimer partner mRNA and protein expression and increased phosphorylation of ERK1/2, JNK, and c-Jun. Specific inhibitors of protein kinase C, extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun

Bile Acids and Salts/*biosynthesis; Cells; Cholesterol 7-alpha-Hydroxylase/*biosynthesis; Cultured; Hepatocyte Growth Factor/*metabolism; Hepatocytes/*metabolism; Humans; Signal Transduction

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1993–2002

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