Abstract
Objective: Further knowledge of basic mechanisms that regulate liver regeneration may help to find therapies to increase otherwise insufficient liver mass. Macrophages are strongly involved in liver regeneration and the chemokine receptor CCR5 is an important player in the trafficking of these cells. Therefore, we investigated the role of CCR5 in liver regeneration. Methods: We performed a 70% hepatectomy in CCR5 knock-out (KO) and wild-type(wt) mice. Liver tissue was collected at various time points and hepatocyte proliferation was analyzed by immunostaining for Ki67 and presence of macrophages by immunostaining for IBA1. Proliferating cell nuclear antigen (PCNA, a marker of proliferation) was analyzed by Western blotting and chemokines and growth factors were analyzed by RT-PCR. Results: Immunostaining on liver sections showed an increased number of proliferating hepatocytes in CCR5 KO (41.6% ± 9.4) mice compared to wt mice (11.3% ± 6.9) at 48h. Increased PCNA level confirmed enhanced proliferation in KO mice. The number of macrophages at 48h was increased in wt mice (54.9% ± 3.2) compared to KO mice (31.5% ± 3.8). Expression of CCR5 ligands and HGF was increased after hepatectomy. Comparing wt and KO mice, increased expression was observed for TNFalpha in wt type mice at 48h and IL-6 expression in KO mice at 6h after hepatectomy. Conclusion: The chemokine receptor CCR5 is implicated in liver regeneration. A decreased inflammatory environment and increased early expression of IL-6 might be involved in the accelerated regeneration in KO mice. Further investigations are needed to determine how the modifications of inflammatory events observed in CCR5 KO mice are implicated in the increased hepatocyte proliferation.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call