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Role of Hepatocyte Growth Regulators in Liver Regeneration

We have studied whether growth factors, cytokines, hormones, neurotransmitters, and local hormones (autacoids) promote the proliferation of hepatic parenchymal cells (i.e., hepatocytes) using in vitro primary cultured hepatocytes. The indicators used for this purpose include changes in DNA synthesis...

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Detalles Bibliográficos
Autores principales: Kimura, Mitsutoshi, Moteki, Hajime, Ogihara, Masahiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9856461/
https://www.ncbi.nlm.nih.gov/pubmed/36672143
http://dx.doi.org/10.3390/cells12020208
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author Kimura, Mitsutoshi
Moteki, Hajime
Ogihara, Masahiko
author_facet Kimura, Mitsutoshi
Moteki, Hajime
Ogihara, Masahiko
author_sort Kimura, Mitsutoshi
collection PubMed
description We have studied whether growth factors, cytokines, hormones, neurotransmitters, and local hormones (autacoids) promote the proliferation of hepatic parenchymal cells (i.e., hepatocytes) using in vitro primary cultured hepatocytes. The indicators used for this purpose include changes in DNA synthesis activity, nuclear number, cell number, cell cycle, and gene expression. In addition, the intracellular signaling pathways from the plasma membrane receptors to the nucleus have been examined in detail for representative growth-promoting factors that have been found to promote DNA synthesis and cell proliferation of hepatocytes. In examining intracellular signaling pathways, the effects of specific inhibitors of presumed signaling factors involved have been pharmacologically confirmed, and the phosphorylation activities of the signaling factors (e.g., RTK, ERK, mTOR, and p70 S6K) have been evaluated. As a result, it has been found that there are many factors that promote the proliferation of hepatocytes (e.g., HGF, EGF, TGF-α, IL-1β, TNF-α, insulin, growth hormone (GH), prostaglandin (PG)), and serotonin (5-HT)), while there are very few factors (e.g., TGF-β1 and glucocorticoids) that inhibit the effects of growth-promoting factors. We have also found that 5-HT and GH promote the proliferation of hepatocytes via different autocrine factors (e.g., TGF-α and IGF-I, respectively). Using primary cultured hepatocytes, it will be possible to further study the molecular and cellular aspects of liver regeneration.
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spelling pubmed-98564612023-01-21 Role of Hepatocyte Growth Regulators in Liver Regeneration Kimura, Mitsutoshi Moteki, Hajime Ogihara, Masahiko Cells Review We have studied whether growth factors, cytokines, hormones, neurotransmitters, and local hormones (autacoids) promote the proliferation of hepatic parenchymal cells (i.e., hepatocytes) using in vitro primary cultured hepatocytes. The indicators used for this purpose include changes in DNA synthesis activity, nuclear number, cell number, cell cycle, and gene expression. In addition, the intracellular signaling pathways from the plasma membrane receptors to the nucleus have been examined in detail for representative growth-promoting factors that have been found to promote DNA synthesis and cell proliferation of hepatocytes. In examining intracellular signaling pathways, the effects of specific inhibitors of presumed signaling factors involved have been pharmacologically confirmed, and the phosphorylation activities of the signaling factors (e.g., RTK, ERK, mTOR, and p70 S6K) have been evaluated. As a result, it has been found that there are many factors that promote the proliferation of hepatocytes (e.g., HGF, EGF, TGF-α, IL-1β, TNF-α, insulin, growth hormone (GH), prostaglandin (PG)), and serotonin (5-HT)), while there are very few factors (e.g., TGF-β1 and glucocorticoids) that inhibit the effects of growth-promoting factors. We have also found that 5-HT and GH promote the proliferation of hepatocytes via different autocrine factors (e.g., TGF-α and IGF-I, respectively). Using primary cultured hepatocytes, it will be possible to further study the molecular and cellular aspects of liver regeneration. MDPI 2023-01-04 /pmc/articles/PMC9856461/ /pubmed/36672143 http://dx.doi.org/10.3390/cells12020208 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Kimura, Mitsutoshi
Moteki, Hajime
Ogihara, Masahiko
Role of Hepatocyte Growth Regulators in Liver Regeneration
title Role of Hepatocyte Growth Regulators in Liver Regeneration
title_full Role of Hepatocyte Growth Regulators in Liver Regeneration
title_fullStr Role of Hepatocyte Growth Regulators in Liver Regeneration
title_full_unstemmed Role of Hepatocyte Growth Regulators in Liver Regeneration
title_short Role of Hepatocyte Growth Regulators in Liver Regeneration
title_sort role of hepatocyte growth regulators in liver regeneration
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9856461/
https://www.ncbi.nlm.nih.gov/pubmed/36672143
http://dx.doi.org/10.3390/cells12020208
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