%0 Journal Article
%T Regeneration in pig livers by compensatory hyperplasia induces high levels of telomerase activity
%A Henning Wege
%A Anett M¨¹ller
%A Lars M¨¹ller
%A Susan Petri
%A J£¿rg Petersen
%A Christian Hillert
%J Comparative Hepatology
%D 2007
%I BioMed Central
%R 10.1186/1476-5926-6-6
%X 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.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.The human liver possesses a remarkable capability to restore its functional capacity following liver injury by a process termed compensatory hyperplasia [1,2]. Differentiated and normally quiescent hepatocytes are the primary cell type responsible for liver regeneration, especially following partial hepatectomy or administration of carbon tetrachloride in rodent models [3]. As reserve compartment, bipotent hepatic progenitor cells are activated if extensive loss or damage of hepatocytes with an impaired replication capability occurs [4].In most somatic human cells, cellular proliferation is associated with progressive telomere shortening. Telomeres are specialized high-order chromatin structures that protect chromosome ends against degradation by forming molecular caps. In addition to telomere-stabilizing proteins, telomeres consist of tens of kilo bases of telomeric repeats [5,6]. After a certain number of cell divisions, replication-associated telomere shortening renders telomeric caps unstable and chromosome ends unprotected. This results in a dramatic upsurge in chromosomal aberrations. Additionally, cells with unstable chromosome ends activate their DNA damage response machinery with entry into cell cycle exit and replicative senescence, a post-mitotic quiescent
%U http://www.comparative-hepatology.com/content/6/1/6