Study for the role of proteoglycans during tissue repair after acute liver injury

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We investigated the role of proteoglycans (PG) during tissue repair after acute liver injury induced to rats by the administration of D-galactosamine. By immunohistochemical study using anti-heparansulfate antibodies and anti DELTAdi antibodies both heparansulfate-PGs and chondroitin sulfate PGs transiently changed in the early phase of acute liver injury.Heparansulfate-PGs transiently disappeared form hepatocyte at 6h after the initiation of acute liver injury and chondroitinsufate PGs increased in staining bi-phasically ; the early increase was found along sinusoid from 6h to day 3 and the late increase was along fibers appeared in the necrotic area after day 4. Analyzes by northern blotting and in situ hybridization indicated that the late increase of chondroitinsulfate-PGs corresponded to the transcriptional increases of decorin and biglycan, both of which were the member of small chondroitinsulfate/dermatansulfate PGs. The early increase of chondroitinsulfate-PGs was indicated to correspond to the increase of unidentified proteoglycans with molecular weight of 163 kDa and 152 kDa that was identified by anti-DELTAdi antibodies. Such the transient increase of chondroitinsulfate proteoglycans may provide the environment efficient to allow the proliferation, since the mitosis requires cell detachment from the extracellular matrix.While the transiently disappearing heparansulfate-PGs was found by northern blot analysis to be fibroglycan, one of membrane type heparansulfate PGs. It was found by others that fibroglycan was capable to bind hepatocyte growth factor, which was a strong mitogen of hepatocytes. Thus, the disappearance of fibroglycan at an early phase of acute liver injury may provide an environment efficient for the binding of HGF to c-Met, true receptor for HGF,which promote the mitogenic response during tissue repair.