Bone morphogenetic protein 7 is elevated in patients with chronic liver disease and exerts fibrogenic effects on human hepatic stellate cells

被引:62
|
作者
Tacke, Frank
Gaebele, Erwin
Bataille, Frauke
Schwabe, Robert F.
Hellerbrand, Claus
Klebl, Frank
Straub, Rainer H.
Luedde, Tom
Manns, Michael P.
Trautwein, Christian
Brenner, David A.
Juergen, Schoelmerich
Schnabl, Bernd
机构
[1] Columbia Univ, Dept Med, New York, NY 10032 USA
[2] Univ Hosp Aachen, Aachen, Germany
[3] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, D-3000 Hannover, Germany
[4] Univ Regensburg, Dept Internal Med 1, D-8400 Regensburg, Germany
[5] Univ Regensburg, Inst Pathol, D-8400 Regensburg, Germany
[6] Columbia Univ, Med Ctr, Coll Phys & Surg, Dept Med, New York, NY USA
关键词
BMP7; liver fibrosis; hepatic stellate cells; type I collagen;
D O I
10.1007/s10620-007-9758-8
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Hepatic stellate cells (HSCs) are the main extracellular matrix (ECM)-producing cells in liver fibrogenesis. The excessive synthesis of ECM proteins deteriorates hepatic architecture and results in liver fibrosis and cirrhosis. This study investigated the role of bone morphogenetic protein 7 (BMP7) as a member of the transforming growth factor (TGF)-beta superfamily in chronic liver disease. Plasma levels of BMP7 were significantly elevated in patients with chronic liver disease compared with healthy controls. Immunohistochemistry of cirrhotic human liver demonstrated upregulated BMP7 protein expression in hepatocytes as compared with normal human liver. Because gene expression for all putative BMP7 receptors was induced during the culture activation process of primary human HSCs, we studied the effects of BMP7 on hTERT immortalized human HSCs in vitro. BMP7, as expressed and secreted after infection with adenoviruses encoding BMP7 (AdBMP7), increased proliferation of HSCs. The mRNA and protein expression of type I collagen and fibronectin was increased in BMP7-stimulated HSCs. Elevated systemic and hepatic levels of BMP7 in patients with chronic liver disease may contribute to progression of liver fibrogenesis in vivo.
引用
收藏
页码:3404 / 3415
页数:12
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