Related Experiment Video
Updated: Aug 21, 2026
Visualization of Vascular and Parenchymal Regeneration after 70% Partial Hepatectomy in Normal Mice
Published on: September 13, 2016
Urinary matrix metalloproteinases and their endogenous inhibitors predict hepatic regeneration after murine partial
Arin K Greene1, Mark Puder, Roopali Roy
1Department of Surgery and The Vascular Biology Program, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA.
Background:
Matrix metalloproteinases (MMPs) play a key role in extracellular matrix remodeling events associated with hepatic regeneration after partial hepatectomy. We therefore hypothesized that urinary MMPs and their endogenous tissue inhibitors of matrix metalloproteinases (TIMPs) might also provide important information regarding initiation and progression of liver regeneration.
Methods:
Groups of 20 mice underwent sham operations, two-thirds hepatectomy, or treatment with the angiogenesis inhibitor, AGM-1470,O-chloroacetyl-carbamoyl-fumagillol (TNP-470), after two-thirds hepatectomy to prevent hepatic regeneration. Urine was collected preoperatively and for 24 days after surgery and tested for MMP-2, MMP-9, TIMP-1, and TIMP-2 using substrate gel electrophoresis (zymography) and Western blot analysis.
Results:
During hepatic regeneration, MMP-9 was detected in the urine at significantly lower levels on postoperative day 8 when the liver returned to its preoperative mass. In contrast, urine from mice whose livers were inhibited from regenerating (TNP-treated groups) contained increased levels of the gelatinases MMP-2 and MMP-9. The MMP inhibitors, TIMP-1 and TIMP-2, were significantly reduced in the urine of mice with normally regenerating livers but were increased in the urine of mice treated with TNP-470 on day 8.
Conclusions:
We demonstrate that (1) urinary MMPs and their cognate inhibitors, the TIMPs, can be detected in the urine of mice undergoing partial hepatectomy, (2) the presence of these remodeling proteins in the urine may predict the progressive return of the partially resected liver to its preoperative mass, and (3) analysis of urinary MMPs and TIMPs may someday provide a noninvasive means of monitoring the status of patients undergoing hepatic resection and transplantation.
Insights
Urinary matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) can indicate liver regeneration after surgery. Monitoring these biomarkers may offer a noninvasive method for assessing liver recovery in patients.
Area of Science:
- Hepatology
- Biochemistry
- Regenerative Medicine
Background:
- Matrix metalloproteinases (MMPs) are crucial for extracellular matrix remodeling during liver regeneration after partial hepatectomy.
- Investigating urinary MMPs and tissue inhibitors of matrix metalloproteinases (TIMPs) may reveal insights into liver regeneration processes.
Purpose of the Study:
- To determine if urinary MMPs and TIMPs can serve as biomarkers for hepatic regeneration following partial hepatectomy.
- To assess the correlation between urinary MMP/TIMP levels and the progression of liver regeneration.
Main Methods:
- Mice underwent sham operations, two-thirds hepatectomy, or hepatectomy with angiogenesis inhibition (TNP-470).
- Urine was collected preoperatively and postoperatively for 24 days.
- Urinary MMP-2, MMP-9, TIMP-1, and TIMP-2 were analyzed using zymography and Western blot.
Main Results:
- Urinary MMP-9 levels decreased during normal liver regeneration.
- Inhibition of regeneration led to increased urinary MMP-2 and MMP-9.
- Urinary TIMP-1 and TIMP-2 levels decreased with normal regeneration but increased when regeneration was inhibited.
Conclusions:
- Urinary MMPs and TIMPs are detectable in mice after partial hepatectomy.
- Urinary MMP and TIMP profiles may predict liver mass recovery.
- Urinary analysis of MMPs and TIMPs could offer a noninvasive method for monitoring patients undergoing liver resection or transplantation.
