The role of Matrix Metalloproteinase‐9 (MMP‐9) in liver regeneration following partial hepatectomy

The liver is a unique organ in that it is able to regenerate following a toxic insult or partial surgical removal. Following partial hepatectomy, hepatocyte proliferation occurs with subsequent matrix remodeling by MMPs including MMP‐2 and MMP‐9. The goal of this study was to determine the role of MMP‐9 between days 2 and 5 following 70% hepatectomy. MMP‐9 +/+ (WT) and MMP‐9 −/− (KO) animals were subjected to partial hepatectomy, then histology, liver weight ratios cell proliferation, cytokine expression, growth factor expression, TUNEL and caspase activation were measured. Histological differences between the WT and KO were seen on days 2 and 5. The KO animals had a significantly decreased rate of weight gain compared to the WT animals. Cellular proliferation as measured by BrdU showed differences with increased staining in WT at days 2 and 5, whereas KO showed an increase at day 3. Multiple cytokines were measured with only TNF‐[alpha] significantly different at day 2. Hepatocyte growth factor was elevated in the WT at days 2 and 3 when compared to KO, however there were no significant differences in TGF‐[beta]. Finally, apoptotic response measured via TUNEL and caspase activation showed significantly less apoptosis in the KO animals. These data indicate that MMP‐9 plays a central role in hepatic regeneration following partial hepatectomy as indicated by these data. This work was supported by the University of Michigan.