Adenovirusmediated overexpression of bone morphogenetic protein9 promotes methionine choline deficiencyinduced nonalcoholic steatohepatitis in nonobese mice.

Liver inflammation and macrophage infiltration are critical steps in the progression of nonalcoholic fatty liver to the development of nonalcoholic steatohepatitis. Bone morphogenetic protein9 is a cytokine involved in the regulation of chemokines and lipogenesis. However, the function of bone morphogenetic protein9 in nonalcoholic steatohepatitis is still unknown. The present study hypothesized that bone morphogenetic protein9 may contribute to steatohepatitis in mice fed a methionine choline deficiency diet (MCD). C57BL/6 mice overexpressing bone morphogenetic protein9 and control mice were fed the MCD diet for 4 weeks. Liver tissue and serum samples were obtained for subsequent measurements. Bone morphogenetic protein9 overexpression exacerbated steatohepatitis in mice on the MCD diet, as indicated by liver histopathology, increased serum alanine aminotransferase activity, aspartate transaminase activity, hepatic inflammatory gene expression and M1 macrophage recruitment. Although bone morphogenetic protein9 overexpression did not affect the expression of profibrogenic genes, including Collagen I (alpha)1 or matrix metalloproteinase (MMP) 9, it did upregulate the expression of transforming growth factorbeta and plasminogen activator inhibitor 1, and downregulated the expression of MMP2. The above results indicate that bone morphogenetic protein9 exerts a proinflammatory role in MCD dietinduced nonalcoholic steatohepatitis.