Thyroid status affects rat liver regeneration after partial hepatectomy by regulating cell cycle and apoptosis proteins

Anna Alisi, Ilaria Demori, Silvana Spagnuolo, Enrico Pierantozzi, Emilia Fugassa, Silvia Leoni

Research output: Contribution to journalArticle

Abstract

In rats, various growth factors and hormones, as well as partial hepatectomy (PH) are able to trigger the proliferative response of hepatocytes. Although recent evidence highlights the important role of thyroid hormones and thyroid status in regulating the growth of liver cells in vitro and in vivo models, the mechanism involved in the pro-proliferative effects of thyroid hormones is still unclear. Here we have investigated how in rats made hypo- and hyperthyroid after prolonged treatment respectively with propylthiouracil (PTU) and triiodothyronine (T3), the thyroid status affects liver regeneration after PH by regulating cell cycle and apoptosis proteins. Our results show that both in control and partially hepatectomized animals hyperthyroidism increases the cyclin D1, E and A levels and the activity of cyclin-cdk complexes, and decreases the levels of cdk inhibitors such as p16 and p27. On the contrary hypothyroidism induces a down-regulation of the activity of cyclin cdk complexes decreasing cyclin levels. Thyroid hormones control also p53 and p73, two proteins involved in apoptosis and growth arrest which are induced by PH. In particular, hypothyroidism increases and T3 treatment decreases p73 levels. The analysis of the phosphorylated forms of p42/44 and p38 MAPK revealed that they are induced during hepatic regeneration in euthyroid and hyperthyroid rats whereas they are negatively regulated in hypothyroid rats. In conclusion our data demonstrate that thyroid status can affects liver regeneration, altering the expression and the activity of the proteins involved in the control of cell cycle and growth arrest.

Original languageEnglish
Pages (from-to)69-76
Number of pages8
JournalCellular Physiology and Biochemistry
Volume15
Issue number1-4
DOIs
Publication statusPublished - 2005

Fingerprint

Cell Cycle Proteins
Liver Regeneration
Hepatectomy
Cyclins
Thyroid Gland
Hyperthyroidism
Thyroid Hormones
Apoptosis
Hypothyroidism
Growth
Propylthiouracil
Cyclin A
Cyclin E
Liver
Mitogen-Activated Protein Kinase 1
Cyclin D1
Triiodothyronine
p38 Mitogen-Activated Protein Kinases
Cell Cycle Checkpoints
Growth Hormone

Keywords

  • Cyclins
  • p53
  • p73
  • Thyroid hormones

ASJC Scopus subject areas

  • Cell Biology
  • Physiology

Cite this

Thyroid status affects rat liver regeneration after partial hepatectomy by regulating cell cycle and apoptosis proteins. / Alisi, Anna; Demori, Ilaria; Spagnuolo, Silvana; Pierantozzi, Enrico; Fugassa, Emilia; Leoni, Silvia.

In: Cellular Physiology and Biochemistry, Vol. 15, No. 1-4, 2005, p. 69-76.

Research output: Contribution to journalArticle

Alisi, Anna ; Demori, Ilaria ; Spagnuolo, Silvana ; Pierantozzi, Enrico ; Fugassa, Emilia ; Leoni, Silvia. / Thyroid status affects rat liver regeneration after partial hepatectomy by regulating cell cycle and apoptosis proteins. In: Cellular Physiology and Biochemistry. 2005 ; Vol. 15, No. 1-4. pp. 69-76.
@article{5e57f4aaf3064a74a857e8f9773375ed,
title = "Thyroid status affects rat liver regeneration after partial hepatectomy by regulating cell cycle and apoptosis proteins",
abstract = "In rats, various growth factors and hormones, as well as partial hepatectomy (PH) are able to trigger the proliferative response of hepatocytes. Although recent evidence highlights the important role of thyroid hormones and thyroid status in regulating the growth of liver cells in vitro and in vivo models, the mechanism involved in the pro-proliferative effects of thyroid hormones is still unclear. Here we have investigated how in rats made hypo- and hyperthyroid after prolonged treatment respectively with propylthiouracil (PTU) and triiodothyronine (T3), the thyroid status affects liver regeneration after PH by regulating cell cycle and apoptosis proteins. Our results show that both in control and partially hepatectomized animals hyperthyroidism increases the cyclin D1, E and A levels and the activity of cyclin-cdk complexes, and decreases the levels of cdk inhibitors such as p16 and p27. On the contrary hypothyroidism induces a down-regulation of the activity of cyclin cdk complexes decreasing cyclin levels. Thyroid hormones control also p53 and p73, two proteins involved in apoptosis and growth arrest which are induced by PH. In particular, hypothyroidism increases and T3 treatment decreases p73 levels. The analysis of the phosphorylated forms of p42/44 and p38 MAPK revealed that they are induced during hepatic regeneration in euthyroid and hyperthyroid rats whereas they are negatively regulated in hypothyroid rats. In conclusion our data demonstrate that thyroid status can affects liver regeneration, altering the expression and the activity of the proteins involved in the control of cell cycle and growth arrest.",
keywords = "Cyclins, p53, p73, Thyroid hormones",
author = "Anna Alisi and Ilaria Demori and Silvana Spagnuolo and Enrico Pierantozzi and Emilia Fugassa and Silvia Leoni",
year = "2005",
doi = "10.1159/000083639",
language = "English",
volume = "15",
pages = "69--76",
journal = "Cellular Physiology and Biochemistry",
issn = "1015-8987",
publisher = "S. Karger AG",
number = "1-4",

}

TY - JOUR

T1 - Thyroid status affects rat liver regeneration after partial hepatectomy by regulating cell cycle and apoptosis proteins

AU - Alisi, Anna

AU - Demori, Ilaria

AU - Spagnuolo, Silvana

AU - Pierantozzi, Enrico

AU - Fugassa, Emilia

AU - Leoni, Silvia

PY - 2005

Y1 - 2005

N2 - In rats, various growth factors and hormones, as well as partial hepatectomy (PH) are able to trigger the proliferative response of hepatocytes. Although recent evidence highlights the important role of thyroid hormones and thyroid status in regulating the growth of liver cells in vitro and in vivo models, the mechanism involved in the pro-proliferative effects of thyroid hormones is still unclear. Here we have investigated how in rats made hypo- and hyperthyroid after prolonged treatment respectively with propylthiouracil (PTU) and triiodothyronine (T3), the thyroid status affects liver regeneration after PH by regulating cell cycle and apoptosis proteins. Our results show that both in control and partially hepatectomized animals hyperthyroidism increases the cyclin D1, E and A levels and the activity of cyclin-cdk complexes, and decreases the levels of cdk inhibitors such as p16 and p27. On the contrary hypothyroidism induces a down-regulation of the activity of cyclin cdk complexes decreasing cyclin levels. Thyroid hormones control also p53 and p73, two proteins involved in apoptosis and growth arrest which are induced by PH. In particular, hypothyroidism increases and T3 treatment decreases p73 levels. The analysis of the phosphorylated forms of p42/44 and p38 MAPK revealed that they are induced during hepatic regeneration in euthyroid and hyperthyroid rats whereas they are negatively regulated in hypothyroid rats. In conclusion our data demonstrate that thyroid status can affects liver regeneration, altering the expression and the activity of the proteins involved in the control of cell cycle and growth arrest.

AB - In rats, various growth factors and hormones, as well as partial hepatectomy (PH) are able to trigger the proliferative response of hepatocytes. Although recent evidence highlights the important role of thyroid hormones and thyroid status in regulating the growth of liver cells in vitro and in vivo models, the mechanism involved in the pro-proliferative effects of thyroid hormones is still unclear. Here we have investigated how in rats made hypo- and hyperthyroid after prolonged treatment respectively with propylthiouracil (PTU) and triiodothyronine (T3), the thyroid status affects liver regeneration after PH by regulating cell cycle and apoptosis proteins. Our results show that both in control and partially hepatectomized animals hyperthyroidism increases the cyclin D1, E and A levels and the activity of cyclin-cdk complexes, and decreases the levels of cdk inhibitors such as p16 and p27. On the contrary hypothyroidism induces a down-regulation of the activity of cyclin cdk complexes decreasing cyclin levels. Thyroid hormones control also p53 and p73, two proteins involved in apoptosis and growth arrest which are induced by PH. In particular, hypothyroidism increases and T3 treatment decreases p73 levels. The analysis of the phosphorylated forms of p42/44 and p38 MAPK revealed that they are induced during hepatic regeneration in euthyroid and hyperthyroid rats whereas they are negatively regulated in hypothyroid rats. In conclusion our data demonstrate that thyroid status can affects liver regeneration, altering the expression and the activity of the proteins involved in the control of cell cycle and growth arrest.

KW - Cyclins

KW - p53

KW - p73

KW - Thyroid hormones

UR - http://www.scopus.com/inward/record.url?scp=12444338831&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=12444338831&partnerID=8YFLogxK

U2 - 10.1159/000083639

DO - 10.1159/000083639

M3 - Article

C2 - 15665517

AN - SCOPUS:12444338831

VL - 15

SP - 69

EP - 76

JO - Cellular Physiology and Biochemistry

JF - Cellular Physiology and Biochemistry

SN - 1015-8987

IS - 1-4

ER -