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GH receptor plays a major role in liver regeneration through the control of EGFR and ERK1/2 activation.

Abstract：

:GH is a pleiotropic hormone that plays a major role in proliferation, differentiation, and metabolism via its specific receptor. It has been previously suggested that GH signaling pathways are required for normal liver regeneration but the molecular mechanisms involved have yet to be determined. The aim of this study was to identify the mechanisms by which GH controls liver regeneration. We performed two thirds partial hepatectomies in GH receptor (GHR)-deficient mice and wild-type littermates and showed a blunted progression in the G(1)/S transition phase of the mutant hepatocytes. This impaired liver regeneration was not corrected by reestablishing IGF-1 expression. Although the initial response to partial hepatectomy at the priming phase appeared to be similar between mutant and wild-type mice, cell cycle progression was significantly blunted in mutant mice. The main defect in GHR-deficient mice was the deficiency of the epidermal growth factor receptor activation during the process of liver regeneration. Finally, among the pathways activated downstream of GHR during G(1) phase progression, namely Erk1/2, Akt, and signal transducer and activator of transcription 3, we only found a reduced Erk1/2 phosphorylation in mutant mice. In conclusion, our results demonstrate that GH signaling plays a major role in liver regeneration and strongly suggest that it acts through the activation of both epidermal growth factor receptor and Erk1/2 pathways.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Zerrad-Saadi A,Lambert-Blot M,Mitchell C,Bretes H,Collin de l'Hortet A,Baud V,Chereau F,Sotiropoulos A,Kopchick JJ,Liao L,Xu J,Gilgenkrantz H,Guidotti JE

doi

10.1210/en.2010-1193

subject

Has Abstract

pub_date

2011-07-01 00:00:00

pages

2731-41

issue

7

eissn

0013-7227

issn

1945-7170

pii

en.2010-1193

journal_volume

152

pub_type

杂志文章

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