Cell-specific expression of hepatocyte growth factor in liver. Upregulation in sinusoidal endothelial cells after carbon tetrachloride.
The cellular origin of hepatocyte growth factor (HGF), a polypeptide implicated in liver regeneration, was examined in normal liver and in hepatic regeneration induced by carbon tetrachloride. In normal liver, HGF and its mRNA were abundant in lipocytes, with smaller amounts present also in sinusoidal endothelial and Kupffer cells. In regenerating liver, HGF gene expression increased exclusively in endothelial cells. HGF mRNA levels rose sixfold in these cells, peaking at 6 h after toxin administration and returning to near normal by 24 h. The rise in HGF mRNA was accompanied by a 5.4-fold increase in HGF secretion. CCl4 did not alter HGF expression by either Kupffer cells or lipocytes; nor did it induce HGF expression by hepatocytes. Nonparenchymal liver cells contained two HGF transcripts: one predicting a full-length molecule of 728 amino acids; and the other encoding a functional five-amino acid deletion variant of HGF. The variant was less abundant than the full-length transcript, but increased in parallel with native HGF mRNA in response to CCl4. The response of nonparenchymal cells to HGF was examined by plating endothelial cells and lipocytes in the presence of recombinant human HGF. Under the conditions examined, the growth factor exerted neither mitogenic nor scatter factor activity on these cells.
Maher
J J
JJ
Liver Core Center, University of California, San Francisco 94110.
D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D002469:Cell Separation; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication; D004727:Endothelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D017228:Hepatocyte Growth Factor / Q000032:analysis / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D007728:Kupffer Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008115:Liver Regeneration; D008297:Male; D012313:RNA / Q000302:isolation & purification / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology; D017384:Sequence Deletion; D013936:Thymidine / Q000378:metabolism; D014158:Transcription, Genetic
D012333:RNA, Messenger; D011994:Recombinant Proteins; D012313:RNA; D017228:Hepatocyte Growth Factor; D004247:DNA; D002251:Carbon Tetrachloride; D013936:Thymidine