Bone morphogenetic protein 7 is elevated in patients with chronic liver disease and exerts fibrogenic effects on human hepatic stellate cells.
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.
Tacke
Frank
F
Medical Clinic III, University Hospital Aachen, Aachen, Germany.
Gäbele
Erwin
E
Bataille
Frauke
F
Schwabe
Robert F
RF
Hellerbrand
Claus
C
Klebl
Frank
F
Straub
Rainer H
RH
Luedde
Tom
T
Manns
Michael P
MP
Trautwein
Christian
C
Brenner
David A
DA
Schölmerich
Jürgen
J
Schnabl
Bernd
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018450:Disease Progression; D015870:Gene Expression / Q000235:genetics; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D018696:Neuroprotective Agents; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta