Regeneration in pig livers by compensatory hyperplasia induces high levels of telomerase activity

Henning Wege¹ , Anett Müller² , Lars Müller² , Susan Petri³ , Jörg Petersen¹ and Christian Hillert²

¹Department of Gastroenterology and Hepatology with Sections Infectious Disease and Tropical Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany

²Department of Hepatobiliary Surgery and Visceral Transplantation, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany

³Department of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany

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Comparative Hepatology 2007, 6:6doi:10.1186/1476-5926-6-6


Published:	2 July 2007

Abstract

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.