Peroxisome Proliferator-Activated Receptor gamma negatively regulates liver regeneration after partial hepatectomy via the HGF/c-Met/ERK1/2 pathways

Abstract Peroxisome Proliferator-Activated Receptor gamma (PPARγ) is a nuclear receptor demonstrated to play an important role in various biological processes. The aim of this study was to determine the effect of PPARγ on liver regeneration upon partial hepatectomy (PH) in mice. Mice were subjected...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Zhangjun Cheng, Lei Liu, Xue-Jun Zhang, Miao Lu, Yang Wang, Volker Assfalg, Melanie Laschinger, Guido von Figura, Yoshiaki Sunami, Christoph W. Michalski, Jörg Kleeff, Helmut Friess, Daniel Hartmann, Norbert Hüser
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ecb71ae021a447b3b0068caed178e122
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ecb71ae021a447b3b0068caed178e122
record_format	dspace
spelling	oai:doaj.org-article:ecb71ae021a447b3b0068caed178e1222021-12-02T15:07:50ZPeroxisome Proliferator-Activated Receptor gamma negatively regulates liver regeneration after partial hepatectomy via the HGF/c-Met/ERK1/2 pathways10.1038/s41598-018-30426-52045-2322https://doaj.org/article/ecb71ae021a447b3b0068caed178e1222018-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-30426-5https://doaj.org/toc/2045-2322Abstract Peroxisome Proliferator-Activated Receptor gamma (PPARγ) is a nuclear receptor demonstrated to play an important role in various biological processes. The aim of this study was to determine the effect of PPARγ on liver regeneration upon partial hepatectomy (PH) in mice. Mice were subjected to two-thirds PH. Before surgery, mice were either treated with the PPARγ agonist rosiglitazone, the PPARγ antagonist GW9662 alone, or with the c-met inhibitor SGX523. Liver-to-body-weight ratio, lab values, and proliferation markers were assessed. Components of the PPARγ-specific signaling pathway were identified by western blot and qRT-PCR. Our results show that liver regeneration is being inhibited by rosiglitazone and accelerated by GW9662. Inhibition of c-Met by SGX523 treatment abrogates GW9662-induced liver regeneration and hepatocyte proliferation. Hepatocyte growth factor (HGF) protein levels were significantly downregulated after rosiglitazone treatment. Activation of HGF/c-Met pathways by phosphorylation of c-Met and ERK1/2 were inhibited in rosiglitazone-treated mice. In turn, blocking phosphorylation of c-Met significantly abrogated the augmented effect of GW9662 on liver regeneration. Our data support the concept that PPARγ abrogates liver growth and hepatocellular proliferation by inhibition of the HGF/c-Met/ERK1/2 pathways. These pathways may represent potential targets in response to liver disease and could impact on the development of molecular therapies.Zhangjun ChengLei LiuXue-Jun ZhangMiao LuYang WangVolker AssfalgMelanie LaschingerGuido von FiguraYoshiaki SunamiChristoph W. MichalskiJörg KleeffHelmut FriessDaniel HartmannNorbert HüserNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zhangjun Cheng Lei Liu Xue-Jun Zhang Miao Lu Yang Wang Volker Assfalg Melanie Laschinger Guido von Figura Yoshiaki Sunami Christoph W. Michalski Jörg Kleeff Helmut Friess Daniel Hartmann Norbert Hüser Peroxisome Proliferator-Activated Receptor gamma negatively regulates liver regeneration after partial hepatectomy via the HGF/c-Met/ERK1/2 pathways
description	Abstract Peroxisome Proliferator-Activated Receptor gamma (PPARγ) is a nuclear receptor demonstrated to play an important role in various biological processes. The aim of this study was to determine the effect of PPARγ on liver regeneration upon partial hepatectomy (PH) in mice. Mice were subjected to two-thirds PH. Before surgery, mice were either treated with the PPARγ agonist rosiglitazone, the PPARγ antagonist GW9662 alone, or with the c-met inhibitor SGX523. Liver-to-body-weight ratio, lab values, and proliferation markers were assessed. Components of the PPARγ-specific signaling pathway were identified by western blot and qRT-PCR. Our results show that liver regeneration is being inhibited by rosiglitazone and accelerated by GW9662. Inhibition of c-Met by SGX523 treatment abrogates GW9662-induced liver regeneration and hepatocyte proliferation. Hepatocyte growth factor (HGF) protein levels were significantly downregulated after rosiglitazone treatment. Activation of HGF/c-Met pathways by phosphorylation of c-Met and ERK1/2 were inhibited in rosiglitazone-treated mice. In turn, blocking phosphorylation of c-Met significantly abrogated the augmented effect of GW9662 on liver regeneration. Our data support the concept that PPARγ abrogates liver growth and hepatocellular proliferation by inhibition of the HGF/c-Met/ERK1/2 pathways. These pathways may represent potential targets in response to liver disease and could impact on the development of molecular therapies.
format	article
author	Zhangjun Cheng Lei Liu Xue-Jun Zhang Miao Lu Yang Wang Volker Assfalg Melanie Laschinger Guido von Figura Yoshiaki Sunami Christoph W. Michalski Jörg Kleeff Helmut Friess Daniel Hartmann Norbert Hüser
author_facet	Zhangjun Cheng Lei Liu Xue-Jun Zhang Miao Lu Yang Wang Volker Assfalg Melanie Laschinger Guido von Figura Yoshiaki Sunami Christoph W. Michalski Jörg Kleeff Helmut Friess Daniel Hartmann Norbert Hüser
author_sort	Zhangjun Cheng
title	Peroxisome Proliferator-Activated Receptor gamma negatively regulates liver regeneration after partial hepatectomy via the HGF/c-Met/ERK1/2 pathways
title_short	Peroxisome Proliferator-Activated Receptor gamma negatively regulates liver regeneration after partial hepatectomy via the HGF/c-Met/ERK1/2 pathways
title_full	Peroxisome Proliferator-Activated Receptor gamma negatively regulates liver regeneration after partial hepatectomy via the HGF/c-Met/ERK1/2 pathways
title_fullStr	Peroxisome Proliferator-Activated Receptor gamma negatively regulates liver regeneration after partial hepatectomy via the HGF/c-Met/ERK1/2 pathways
title_full_unstemmed	Peroxisome Proliferator-Activated Receptor gamma negatively regulates liver regeneration after partial hepatectomy via the HGF/c-Met/ERK1/2 pathways
title_sort	peroxisome proliferator-activated receptor gamma negatively regulates liver regeneration after partial hepatectomy via the hgf/c-met/erk1/2 pathways
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/ecb71ae021a447b3b0068caed178e122
work_keys_str_mv	AT zhangjuncheng peroxisomeproliferatoractivatedreceptorgammanegativelyregulatesliverregenerationafterpartialhepatectomyviathehgfcmeterk12pathways AT leiliu peroxisomeproliferatoractivatedreceptorgammanegativelyregulatesliverregenerationafterpartialhepatectomyviathehgfcmeterk12pathways AT xuejunzhang peroxisomeproliferatoractivatedreceptorgammanegativelyregulatesliverregenerationafterpartialhepatectomyviathehgfcmeterk12pathways AT miaolu peroxisomeproliferatoractivatedreceptorgammanegativelyregulatesliverregenerationafterpartialhepatectomyviathehgfcmeterk12pathways AT yangwang peroxisomeproliferatoractivatedreceptorgammanegativelyregulatesliverregenerationafterpartialhepatectomyviathehgfcmeterk12pathways AT volkerassfalg peroxisomeproliferatoractivatedreceptorgammanegativelyregulatesliverregenerationafterpartialhepatectomyviathehgfcmeterk12pathways AT melanielaschinger peroxisomeproliferatoractivatedreceptorgammanegativelyregulatesliverregenerationafterpartialhepatectomyviathehgfcmeterk12pathways AT guidovonfigura peroxisomeproliferatoractivatedreceptorgammanegativelyregulatesliverregenerationafterpartialhepatectomyviathehgfcmeterk12pathways AT yoshiakisunami peroxisomeproliferatoractivatedreceptorgammanegativelyregulatesliverregenerationafterpartialhepatectomyviathehgfcmeterk12pathways AT christophwmichalski peroxisomeproliferatoractivatedreceptorgammanegativelyregulatesliverregenerationafterpartialhepatectomyviathehgfcmeterk12pathways AT jorgkleeff peroxisomeproliferatoractivatedreceptorgammanegativelyregulatesliverregenerationafterpartialhepatectomyviathehgfcmeterk12pathways AT helmutfriess peroxisomeproliferatoractivatedreceptorgammanegativelyregulatesliverregenerationafterpartialhepatectomyviathehgfcmeterk12pathways AT danielhartmann peroxisomeproliferatoractivatedreceptorgammanegativelyregulatesliverregenerationafterpartialhepatectomyviathehgfcmeterk12pathways AT norberthuser peroxisomeproliferatoractivatedreceptorgammanegativelyregulatesliverregenerationafterpartialhepatectomyviathehgfcmeterk12pathways
_version_	1718388422519816192

Peroxisome Proliferator-Activated Receptor gamma negatively regulates liver regeneration after partial hepatectomy via the HGF/c-Met/ERK1/2 pathways

Ejemplares similares