Growth-Related Signaling Regulates Activation of Telomerase in Regenerating Hepatocytes

Inui, Takuo; Shinomiya, Nariyoshi; Fukasawa, Masashi; Kobayashi, Megumi; Kuranaga, Noritsugu; Ohkura, Shuri; Seki, Shu

doi:10.1006/excr.2001.5446

Cited by 33 publications

(39 citation statements)

References 35 publications

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“…Hepatocyte telomere length is shortened during each cell division, a process that limits the lifespan of primary human cells in vitro. 14,15 This process is accelerated during viral hepatitis. Hepatocyte telomere shortening and senescence have been convincingly shown to correlate with progression of fibrosis in humans.…”

Section: Lend New Weight To An Established Conceptmentioning

confidence: 99%

The impact of advancing donor age on histologic recurrence of hepatitis C infection: The perils of ignored maternal advice

Charlton

2003

Liver Transpl

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Recurrent hepatitis occurs in the majority of patients undergoing liver transplantation for hepatitis C virus (HCV) cirrhosis, with progression to cirrhosis in up to 30% after 5 years. Based on these data, a decrease in survival can be anticipated with prolonged follow-up. Furthermore, posttransplantation HCV-fibrosis progression has been shown in recent years to increase. Our aims were (1) to describe the natural history of HCV-infected recipients, particularly to determine whether survival has decreased in recent years; (2) to compare this outcome with that observed in non-HCV-infected cirrhosis controls; and (3) to determine the factors associated with disease severity and survival. Among 522 cirrhotic patients undergoing transplantation between 1991 and 2000, 283 (54%) were infected with HCV. Yearly biopsies were performed in these recipients and at 1 and 5 years in the remainder. With similar follow-up, the percentage of deaths in the HCV(؉) group was significantly higher than in the HCV-group (37% vs. 22%, P <.001), and patient survival was lower (77%, 61%, 55% vs. 87%, 76%, 70% at 1, 5, and 7 years, respectively; P ‫.)1000.؍‬ Although survival has increased in the HCV-group in recent years, it has significantly decreased in HCV recipients (P <.0001). The main cause of death among the latter was decompensated graft cirrhosis (n ‫؍‬ 23/105, 22%), whereas that of HCV-patients was infections (n ‫؍‬ 10/52, 19%). Reasons for the recent worse outcome in HCV؉ recipients include the increased donor age and stronger immunosuppression. In conclusion, patient survival is lower among HCV؉ recipients than among HCV-ones and has been decreasing in recent years. The aging of donors is a major contributor to this worse outcome.Advancing donor liver age and rapid fibrosis progression following transplantation for hepatitis C.

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Section: Lend New Weight To An Established Conceptmentioning

confidence: 99%

The impact of advancing donor age on histologic recurrence of hepatitis C infection: The perils of ignored maternal advice

Charlton

2003

Liver Transpl

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“…10 Previous reports on telomerase activity during experimental liver regeneration studies in mice and rat delivered inconsistent results. [11][12][13] A major problem in these studies is that rodents, in particular mice, show a more ubiquitous expression of telomerase as compared to humans.…”

Section: Introductionmentioning

confidence: 99%

The Promoter of Human Telomerase Reverse Transcriptase Is Activated During Liver Regeneration and Hepatocyte Proliferation

et al. 2011

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“…In a primary culture of rat hepatocytes, which express GHR physiologically, we found that GH also triggered telomerase activity. Previously it has been shown that other growth factors such as EGF and hepatocyte growth factor also induce telomerase activation in hepatocytes (Inui et al 2002). These events would confirm the regulation of telomerase by different growth factors, among which would be GH.…”

Section: Discussionmentioning

confidence: 58%

“…Human somatic cells normally lack telomerase activity (Ramakrishnan et al 1998); however, approximately 90% of tumour-derived immortal cells (Kim et al 1994), the germline cells, certain stem cells and cells from renewable tissues, such as intestinal epithelium and liver (Wright et al 1996, Yasumoto et al 1996, Inui et al 2002, do contain telomerase activity. In these cells, telomerase activity is usually growth-regulated.…”

Section: Introductionmentioning

confidence: 99%

Direct activation of telomerase by GH via phosphatidylinositol 3′-kinase

Gómez-García

Sánchez²,

Vallejo‐Cremades³

et al. 2005

Journal of Endocrinology

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Telomerase is a ribonucleoprotein DNA polymerase that has been associated with cell proliferation, cell survival and apoptosis inhibition. Telomerase is regulated by specific growth factors, cytokines and hormones. The present study examines the effect of GH on telomerase activity and identifies the signal transduction pathway involved in this process in Chinese hamster ovary (CHO)4 cells, which express rat GH receptor cDNA. Telomeric repeat amplification protocol assays demonstrated that treating CHO4 cells with increasingly high doses of GH up-regulated telomerase activity with the maximum activation at 24 h. Similarly, GH activated telomerase in another cell system, primary cultures of rat hepatocytes. The telomerase activation in CHO4 cells was produced with an increase in hamster telomerase catalytic subunit (hamTERT) mRNA expression. The telomerase activity induced by GH was specifically blocked by the phosphatidylinositol 3 -kinase (PI3-K) inhibitor, LY294002, but not by the MAP kinase kinase inhibitor, PD98059. These findings suggest that GH could activate telomerase through the direct activation of TERT transcription, as well as through the PI3-K signalling pathway.

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Growth-Related Signaling Regulates Activation of Telomerase in Regenerating Hepatocytes

Cited by 33 publications

References 35 publications

The impact of advancing donor age on histologic recurrence of hepatitis C infection: The perils of ignored maternal advice

The impact of advancing donor age on histologic recurrence of hepatitis C infection: The perils of ignored maternal advice

The Promoter of Human Telomerase Reverse Transcriptase Is Activated During Liver Regeneration and Hepatocyte Proliferation

Direct activation of telomerase by GH via phosphatidylinositol 3′-kinase

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