PB0909 - TREM-Like Transcript-1, a platelet receptor, as a potential regulator of hepatic regeneration post-surgical resection

Background: Liver resection is not an uncommon treatment of cancer. The successful regeneration of liver tissue has been found to correlate with platelet accumulation and fibrinogen deposition. Patients without sufficient fibrinogen deposition have reduced hepatic regenerative potential and are associated with poor prognosis. The platelet receptor, TREM-Like Transcript-1 (TLT-1), binds fibrinogen and mediates platelet and fibrinogen deposition during lung injury. We hypothesize that TLT-1, being a ligand for fibrinogen, mediates fibrinogen deposition after liver resection and positively regulates post-surgical regeneration of hepatic tissue and survival.

Aims: Determine whether TLT-1 plays a critical role in regulating hepatic regeneration.

Methods: We are performing 70% partial hepatectomy (removal of left lateral, medial and quadrate lobe) and evaluating the right lateral lobe at 30 minutes, or at 7 days post-surgery for platelet adhesion, fibrinogen deposition by immunohistochemistry and survival as primary endpoints in wild type and treml1-/- mice. Secondary parameters include cytokine measurement and evaluation of the molecular pathways in liver by western blot.

Results: Fluorescent stained hepatic tissue was imaged with a 2-photon microscope after initial and at a 30-minute time point after 70% resection. IHC analysis demonstrates that treml1-/- mice have decreased platelet accumulation and fibrinogen deposition in the hepatic tissue compared to wildtype controls, suggesting that TLT-1 plays a role in regulating fibrinogen deposition and platelet accumulation in hepatic tissue during the acute phase response. We are currently conducting a recovery 7-day trial to determine whether the is a difference in mortality, preliminary data suggests that treml1-/- mice are more susceptible to mortality over a 7-day time course (n=4, 3 dead) compared to wild type controls (n=3, 1 dead p=0.140) (Figure 1).

Conclusion(s): Preliminary results suggest that similar to our lung injury model, TLT-1 regulates platelet and fibrinogen affects survival. Our poster will report the current state of these studies.