Amino acid-induced regulation of hepatocyte growth: possible role of Drosha
Identifieur interne : 000063 ( France/Analysis ); précédent : 000062; suivant : 000064Amino acid-induced regulation of hepatocyte growth: possible role of Drosha
Auteurs : Gaia Fabris [France] ; Olivier Dumortier [France] ; Didier F. Pisani [France] ; Nadine Gautier [France] ; Emmanuel Van Obberghen [France]Source :
- Cell Death & Disease [ 2041-4889 ] ; 2019.
Abstract
In an adult healthy liver, hepatocytes are in a quiescent stage unless a physical injury, such as ablation, or a toxic attack occur. Indeed, to maintain their crucial organismal homeostatic role, the damaged or remaining hepatocytes will start proliferating to restore their functional mass. One of the limiting conditions for cell proliferation is amino-acid availability, necessary both for the synthesis of proteins important for cell growth and division, and for the activation of the mTOR pathway, known for its considerable role in the regulation of cell proliferation. The overarching aim of our present work was to investigate the role of amino acids in the regulation of the switch between quiescence and growth of adult hepatocytes. To do so we used non-confluent primary adult rat hepatocytes as a model of partially ablated liver. We discovered that the absence of amino acids induces in primary rat hepatocytes the entrance in a quiescence state together with an increase in Drosha protein, which does not involve the mTOR pathway. Conversely, Drosha knockdown allows the hepatocytes, quiescent after amino-acid deprivation, to proliferate again. Further, hepatocyte proliferation appears to be independent of miRNAs, the canonical downstream partners of Drosha. Taken together, our observations reveal an intriguing non-canonical action of Drosha in the control of growth regulation of adult hepatocytes responding to a nutritional strain, and they may help to design novel preventive and/or therapeutic approaches for hepatic failure.
Url:
DOI: 10.1038/s41419-019-1779-7
PubMed: 31332188
PubMed Central: 6646398
Affiliations:
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PMC:6646398Le document en format XML
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<front><div type="abstract" xml:lang="en"><p id="Par1">In an adult healthy liver, hepatocytes are in a quiescent stage unless a physical injury, such as ablation, or a toxic attack occur. Indeed, to maintain their crucial organismal homeostatic role, the damaged or remaining hepatocytes will start proliferating to restore their functional mass. One of the limiting conditions for cell proliferation is amino-acid availability, necessary both for the synthesis of proteins important for cell growth and division, and for the activation of the mTOR pathway, known for its considerable role in the regulation of cell proliferation. The overarching aim of our present work was to investigate the role of amino acids in the regulation of the switch between quiescence and growth of adult hepatocytes. To do so we used non-confluent primary adult rat hepatocytes as a model of partially ablated liver. We discovered that the absence of amino acids induces in primary rat hepatocytes the entrance in a quiescence state together with an increase in Drosha protein, which does not involve the mTOR pathway. Conversely, Drosha knockdown allows the hepatocytes, quiescent after amino-acid deprivation, to proliferate again. Further, hepatocyte proliferation appears to be independent of miRNAs, the canonical downstream partners of Drosha. Taken together, our observations reveal an intriguing non-canonical action of Drosha in the control of growth regulation of adult hepatocytes responding to a nutritional strain, and they may help to design novel preventive and/or therapeutic approaches for hepatic failure.</p>
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<author><name sortKey="Bollati, V" uniqKey="Bollati V">V Bollati</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Voskarides, K" uniqKey="Voskarides K">K Voskarides</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hock, J" uniqKey="Hock J">J Höck</name>
</author>
<author><name sortKey="Meister, G" uniqKey="Meister G">G Meister</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Benjamin, C" uniqKey="Benjamin C">C Benjamin</name>
</author>
<author><name sortKey="Gregory, J" uniqKey="Gregory J">J Gregory</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Liu, J" uniqKey="Liu J">J Liu</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Fehlmann, M" uniqKey="Fehlmann M">M Fehlmann</name>
</author>
<author><name sortKey="Le Cam, A" uniqKey="Le Cam A">A Le Cam</name>
</author>
<author><name sortKey="Freychet, P" uniqKey="Freychet P">P Freychet</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Brand, Md" uniqKey="Brand M">MD Brand</name>
</author>
<author><name sortKey="Nicholls, Dg" uniqKey="Nicholls D">DG Nicholls</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
</TEI>
<affiliations><list><country><li>France</li>
</country>
<region><li>Provence-Alpes-Côte d'Azur</li>
</region>
<settlement><li>Nice</li>
</settlement>
</list>
<tree><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Fabris, Gaia" sort="Fabris, Gaia" uniqKey="Fabris G" first="Gaia" last="Fabris">Gaia Fabris</name>
</region>
<name sortKey="Dumortier, Olivier" sort="Dumortier, Olivier" uniqKey="Dumortier O" first="Olivier" last="Dumortier">Olivier Dumortier</name>
<name sortKey="Fabris, Gaia" sort="Fabris, Gaia" uniqKey="Fabris G" first="Gaia" last="Fabris">Gaia Fabris</name>
<name sortKey="Gautier, Nadine" sort="Gautier, Nadine" uniqKey="Gautier N" first="Nadine" last="Gautier">Nadine Gautier</name>
<name sortKey="Gautier, Nadine" sort="Gautier, Nadine" uniqKey="Gautier N" first="Nadine" last="Gautier">Nadine Gautier</name>
<name sortKey="Pisani, Didier F" sort="Pisani, Didier F" uniqKey="Pisani D" first="Didier F." last="Pisani">Didier F. Pisani</name>
<name sortKey="Van Obberghen, Emmanuel" sort="Van Obberghen, Emmanuel" uniqKey="Van Obberghen E" first="Emmanuel" last="Van Obberghen">Emmanuel Van Obberghen</name>
<name sortKey="Van Obberghen, Emmanuel" sort="Van Obberghen, Emmanuel" uniqKey="Van Obberghen E" first="Emmanuel" last="Van Obberghen">Emmanuel Van Obberghen</name>
</country>
</tree>
</affiliations>
</record>
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