Influence of Telomere Length in Hepatocytes on Liver Regeneration after Partial Hepatectomy in Rats

Anne Andert; Hamid P. Alizai; Tom Florian Ulmer; Christoph Heidenhain; Patrick Ziegler; Tim H. Bruemmendorf; Ulf Peter Neumann; Fabian Beier; Christian D. Klink

doi:10.1159/000489090

Influence of Telomere Length in Hepatocytes on Liver Regeneration after Partial Hepatectomy in Rats

Anne Andert^*, Hamid P. Alizai, Tom Florian Ulmer, Christoph Heidenhain, Patrick Ziegler, Tim H. Bruemmendorf, Ulf Peter Neumann, Fabian Beier, Christian D. Klink

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background: The aim of this study was to investigate telomere length in hepatocytes as a biomarker for liver regeneration after partial hepatectomy (PH) in rats. Materials and Methods: Sixty male Wistar rats underwent a 70% PH. One-month-old rats were assigned to group Y (n = 30) and 4-month-old rats were assigned to group O (n = 30). The rats were euthanized, and their livers were then harvested at postoperative day (POD) 1, 2, 3, 4, or 7. Telomere lengths and established parameters for liver regeneration (residual liver weight and levels of proliferating cell nuclear antigen [PCNA], Ki67, and interleukin [IL]-6) were measured. Results: We observed a significant increase in residual liver weight in group Y compared to that in group O (p = 0.001). The levels of Ki67 (p = 0.016), PCNA (p <0.0001), and IL-6 (p <0.001) were significantly higher in group Y. Furthermore, the rats in group Y had significantly earlier peak values of Ki67 and PCNA. Telomeres were significantly longer at the time of PH in group Y (p = 0.001). We showed a correlation between telomere length at the day of PH and liver regeneration. Animals with longer telomeres at the time of PH had better liver regeneration (p = 0.015). In group Y, animals with increased liver regeneration (median cut-off: >122%) did not show any significant difference in telomere length (p = 0.587) compared to rats with regular regeneration (<122%). However, in the older animals, rats with increased regeneration had significantly longer telomeres (p = 0.019) than rats with regular regeneration. Conclusion: Telomere length in rat hepatocytes depends on age, and animals with long telomeres had earlier and better regeneration of healthy liver tissue than rats with short telomeres. Our data confirms that telomere length in rat hepatocytes could be used as a possible predictive marker for liver regeneration, and could help to identify older individuals with a high capacity for hepatic regeneration. (C) 2018 S. Karger AG, Basel

Original language	English
Pages (from-to)	83-90
Number of pages	8
Journal	European Surgical Research
Volume	59
Issue number	1-2
DOIs	https://doi.org/10.1159/000489090
Publication status	Published - 2018

Keywords

Liver surgery
Liver regeneration
Telomere length
CELLULAR SENESCENCE
OXIDATIVE STRESS
REDUCTION
TURNOVER
DYNAMICS
DISEASES
CANCER
CELLS
AGE

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10.1159/000489090

Cite this

@article{487da1baaed443eab9810b2202e5e5cf,

title = "Influence of Telomere Length in Hepatocytes on Liver Regeneration after Partial Hepatectomy in Rats",

abstract = "Background: The aim of this study was to investigate telomere length in hepatocytes as a biomarker for liver regeneration after partial hepatectomy (PH) in rats. Materials and Methods: Sixty male Wistar rats underwent a 70% PH. One-month-old rats were assigned to group Y (n = 30) and 4-month-old rats were assigned to group O (n = 30). The rats were euthanized, and their livers were then harvested at postoperative day (POD) 1, 2, 3, 4, or 7. Telomere lengths and established parameters for liver regeneration (residual liver weight and levels of proliferating cell nuclear antigen [PCNA], Ki67, and interleukin [IL]-6) were measured. Results: We observed a significant increase in residual liver weight in group Y compared to that in group O (p = 0.001). The levels of Ki67 (p = 0.016), PCNA (p <0.0001), and IL-6 (p <0.001) were significantly higher in group Y. Furthermore, the rats in group Y had significantly earlier peak values of Ki67 and PCNA. Telomeres were significantly longer at the time of PH in group Y (p = 0.001). We showed a correlation between telomere length at the day of PH and liver regeneration. Animals with longer telomeres at the time of PH had better liver regeneration (p = 0.015). In group Y, animals with increased liver regeneration (median cut-off: >122%) did not show any significant difference in telomere length (p = 0.587) compared to rats with regular regeneration (<122%). However, in the older animals, rats with increased regeneration had significantly longer telomeres (p = 0.019) than rats with regular regeneration. Conclusion: Telomere length in rat hepatocytes depends on age, and animals with long telomeres had earlier and better regeneration of healthy liver tissue than rats with short telomeres. Our data confirms that telomere length in rat hepatocytes could be used as a possible predictive marker for liver regeneration, and could help to identify older individuals with a high capacity for hepatic regeneration. (C) 2018 S. Karger AG, Basel",

keywords = "Liver surgery, Liver regeneration, Telomere length, CELLULAR SENESCENCE, OXIDATIVE STRESS, REDUCTION, TURNOVER, DYNAMICS, DISEASES, CANCER, CELLS, AGE",

author = "Anne Andert and Alizai, {Hamid P.} and Ulmer, {Tom Florian} and Christoph Heidenhain and Patrick Ziegler and Bruemmendorf, {Tim H.} and Neumann, {Ulf Peter} and Fabian Beier and Klink, {Christian D.}",

year = "2018",

doi = "10.1159/000489090",

language = "English",

volume = "59",

pages = "83--90",

journal = "European Surgical Research",

issn = "0014-312X",

publisher = "Karger",

number = "1-2",

}

TY - JOUR

T1 - Influence of Telomere Length in Hepatocytes on Liver Regeneration after Partial Hepatectomy in Rats

AU - Andert, Anne

AU - Alizai, Hamid P.

AU - Ulmer, Tom Florian

AU - Heidenhain, Christoph

AU - Ziegler, Patrick

AU - Bruemmendorf, Tim H.

AU - Neumann, Ulf Peter

AU - Beier, Fabian

AU - Klink, Christian D.

PY - 2018

Y1 - 2018

N2 - Background: The aim of this study was to investigate telomere length in hepatocytes as a biomarker for liver regeneration after partial hepatectomy (PH) in rats. Materials and Methods: Sixty male Wistar rats underwent a 70% PH. One-month-old rats were assigned to group Y (n = 30) and 4-month-old rats were assigned to group O (n = 30). The rats were euthanized, and their livers were then harvested at postoperative day (POD) 1, 2, 3, 4, or 7. Telomere lengths and established parameters for liver regeneration (residual liver weight and levels of proliferating cell nuclear antigen [PCNA], Ki67, and interleukin [IL]-6) were measured. Results: We observed a significant increase in residual liver weight in group Y compared to that in group O (p = 0.001). The levels of Ki67 (p = 0.016), PCNA (p <0.0001), and IL-6 (p <0.001) were significantly higher in group Y. Furthermore, the rats in group Y had significantly earlier peak values of Ki67 and PCNA. Telomeres were significantly longer at the time of PH in group Y (p = 0.001). We showed a correlation between telomere length at the day of PH and liver regeneration. Animals with longer telomeres at the time of PH had better liver regeneration (p = 0.015). In group Y, animals with increased liver regeneration (median cut-off: >122%) did not show any significant difference in telomere length (p = 0.587) compared to rats with regular regeneration (<122%). However, in the older animals, rats with increased regeneration had significantly longer telomeres (p = 0.019) than rats with regular regeneration. Conclusion: Telomere length in rat hepatocytes depends on age, and animals with long telomeres had earlier and better regeneration of healthy liver tissue than rats with short telomeres. Our data confirms that telomere length in rat hepatocytes could be used as a possible predictive marker for liver regeneration, and could help to identify older individuals with a high capacity for hepatic regeneration. (C) 2018 S. Karger AG, Basel

AB - Background: The aim of this study was to investigate telomere length in hepatocytes as a biomarker for liver regeneration after partial hepatectomy (PH) in rats. Materials and Methods: Sixty male Wistar rats underwent a 70% PH. One-month-old rats were assigned to group Y (n = 30) and 4-month-old rats were assigned to group O (n = 30). The rats were euthanized, and their livers were then harvested at postoperative day (POD) 1, 2, 3, 4, or 7. Telomere lengths and established parameters for liver regeneration (residual liver weight and levels of proliferating cell nuclear antigen [PCNA], Ki67, and interleukin [IL]-6) were measured. Results: We observed a significant increase in residual liver weight in group Y compared to that in group O (p = 0.001). The levels of Ki67 (p = 0.016), PCNA (p <0.0001), and IL-6 (p <0.001) were significantly higher in group Y. Furthermore, the rats in group Y had significantly earlier peak values of Ki67 and PCNA. Telomeres were significantly longer at the time of PH in group Y (p = 0.001). We showed a correlation between telomere length at the day of PH and liver regeneration. Animals with longer telomeres at the time of PH had better liver regeneration (p = 0.015). In group Y, animals with increased liver regeneration (median cut-off: >122%) did not show any significant difference in telomere length (p = 0.587) compared to rats with regular regeneration (<122%). However, in the older animals, rats with increased regeneration had significantly longer telomeres (p = 0.019) than rats with regular regeneration. Conclusion: Telomere length in rat hepatocytes depends on age, and animals with long telomeres had earlier and better regeneration of healthy liver tissue than rats with short telomeres. Our data confirms that telomere length in rat hepatocytes could be used as a possible predictive marker for liver regeneration, and could help to identify older individuals with a high capacity for hepatic regeneration. (C) 2018 S. Karger AG, Basel

KW - Liver surgery

KW - Liver regeneration

KW - Telomere length

KW - CELLULAR SENESCENCE

KW - OXIDATIVE STRESS

KW - REDUCTION

KW - TURNOVER

KW - DYNAMICS

KW - DISEASES

KW - CANCER

KW - CELLS

KW - AGE

U2 - 10.1159/000489090

DO - 10.1159/000489090

M3 - Article

C2 - 29886505

SN - 0014-312X

VL - 59

SP - 83

EP - 90

JO - European Surgical Research

JF - European Surgical Research

IS - 1-2

ER -