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Anti‐hepatocyte growth factor antibody inhibits hepatocyte proliferation during liver regeneration
Author(s) -
Burr Andrew W.,
Toole Kieran,
Chapman Claire,
Hines Julie E.,
Burt Alastair D.
Publication year - 1998
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/(sici)1096-9896(199807)185:3<298::aid-path88>3.0.co;2-b
Subject(s) - hepatocyte growth factor , hepatocyte , in vivo , liver regeneration , medicine , endocrinology , bromodeoxyuridine , carbon tetrachloride , bolus (digestion) , ccl4 , antibody , biology , monoclonal antibody , in vitro , pharmacology , immunology , chemistry , regeneration (biology) , immunohistochemistry , biochemistry , microbiology and biotechnology , receptor , organic chemistry
Abstract In vitro studies have shown hepatocyte growth factor (HGF) to be a potent mitogen for hepatocytes. Direct evidence of a mitogenic role in vivo was sought by inhibiting HGF activity, using continuous administration of neutralizing antibody to rats which had a stimulus for liver regeneration. Alzet osmotic mini‐pumps, administering a constant supply of anti‐HGF monoclonal antibody (clone D9), were inserted intraperitoneally into male Wistar rats; an irrelevant isotypical antibody was administered to controls. Forty‐five animals received an intragastric bolus of 40 per cent carbon tetrachloride (CCl 4 ) and groups of three test and control animals were killed at 24 h intervals for 7 days. Treatment with anti‐HGF monoclonal antibody significantly inhibited the levels of immunodetectable HGF in the sera of rats following CCl 4 administration. In comparison with controls, hepatocyte proliferation as assessed by bromodeoxyuridine labelling in anti‐HGF‐treated animals was significantly inhibited at 24 h ( P <0·001), 48 h ( P <0·001), and 96 h ( P <0·05) post‐CCl 4 administration. In contrast, sinusoidal cell proliferation was not significantly different from controls at any time point. Inhibition of the parenchymal proliferative response to acute CCl 4 ‐induced liver injury by the in vivo neutralization of HGF provides direct evidence that this growth factor plays an important role in liver regeneration following necrosis. © 1998 John Wiley & Sons, Ltd.