Background: Several highly proliferative human cells transiently activate telomerase, a ribonucleoprotein with reverse transcriptase activity, to counterbalance replication-associated telomere erosion and to increase stress resistance. Quiescent human hepatocytes exhibit very low or undetectable levels of telomerase activity. However, hepatocytes display a remarkable proliferative capability following liver injury. To investigate whether liver regeneration by compensatory hyperplasia is associated with telomerase activation, we measured telomerase activity in pig livers after 70 to 80% partial hepatectomy using a fully quantitative real-time telomeric repeat amplification protocol. In contrast to commonly studied inbred laboratory mouse strains, telomere length and telomerase activity in porcine tissues are comparable to humans.
Results: Following partial hepatectomy, histology revealed mitotic hepatocytes as marker for compensatory hyperplasia. As expected, there was no induction of inflammation. Telomerase activity increased significantly showing the highest levels (5-fold upregulation) in pigs treated with partial hepatectomy and hepatic decompression. Moreover, telomerase activity significantly correlated to the number of mitotic hepatocytes.
Conclusion: Our data demonstrate telomerase activation in liver regeneration by compensatory hyperplasia in a large animal model with telomere biology comparable to humans. Telomerase activation may constitute a mechanism to protect proliferating liver cells against telomere shortening and oxidative stress.