Heparanase expression during normal liver development and following partial hepatectomy

Abstract

Heparan sulphate proteoglycans are major components of the liver extracellular matrix. Their cleavage by heparanase (endo-beta-glucuronidase) may thus be involved in liver-specific normal and pathological processes. Heparanase mRNA and protein were expressed during liver development but not in the mature healthy liver. A biphasic gain of heparanase expression, detected by immunostaining, western blotting, and real-time RT-PCR, was clearly noted following partial hepatectomy, peaking at 12 and 96-168 h and subsiding 2 weeks post-surgery. Expression of heparan sulphate gradually increased throughout the regeneration process. Unlike heparanase, baseline levels of matrix metalloproteinase-2 (MMP-2) were detected in the intact liver, increasing up to 4 days following partial hepatectomy and subsiding at day 10. Bands matching MMP-9 were absent prior to hepatectomy, but visible 2 h post-hepatectomy. Thioacetamide-induced liver fibrosis was associated with increased levels of MMP-9 and MMP-2, correlating with the severity of the disease. Elevated heparanase levels were noted in the early stages of fibrosis, with no further increase evident in rats exhibiting higher fibrotic grades. Taken together, these data suggest a role for heparanase during liver development and remodelling.