SPARC expression is associated with hepatic injury in rodents and humans with non-alcoholic fatty liver disease

Abstract Mechanisms that control progression from simple steatosis to steato-hepatitis and fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) are unknown. SPARC, a secreted matricellular protein, is over-expressed in the liver under chronic injury. Contribution of SPARC accumulation...

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Autores principales:	Guillermo Mazzolini, Catalina Atorrasagasti, Agostina Onorato, Estanislao Peixoto, Martin Schlattjan, Jan-Peter Sowa, Svenja Sydor, Guido Gerken, Ali Canbay
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1c427a079f5b42e8bf090c1de65c88de
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spelling	oai:doaj.org-article:1c427a079f5b42e8bf090c1de65c88de2021-12-02T15:08:26ZSPARC expression is associated with hepatic injury in rodents and humans with non-alcoholic fatty liver disease10.1038/s41598-017-18981-92045-2322https://doaj.org/article/1c427a079f5b42e8bf090c1de65c88de2018-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-18981-9https://doaj.org/toc/2045-2322Abstract Mechanisms that control progression from simple steatosis to steato-hepatitis and fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) are unknown. SPARC, a secreted matricellular protein, is over-expressed in the liver under chronic injury. Contribution of SPARC accumulation to disease severity is largely unknown in NAFLD. We assessed the hypothesis that SPARC is increased in livers with more necrosis and inflammation and could be associated with more fibrosis. qrt-PCR, immunohistochemistry, and ELISA were employed to localize and quantify changes in SPARC in 62 morbidly obese patients with NAFLD/NASH and in a mouse model of diet-induced-NASH. Results were correlated with the severity of NAFLD/NASH. In obese patients 2 subgroups were identified with either high SPARC expression (n = 16) or low SPARC expression (n = 46) in the liver, with a cutoff of 1.2 fold expression. High expression of SPARC paralleled hepatocellular damage and increased mRNA expression of pro-fibrogenic factors in the liver. In line with these findings, in the NASH animal model SPARC knockout mice were protected from inflammatory injury, and showed less inflammation and fibrosis. Hepatic SPARC expression is associated with liver injury and fibrogenic processes in NAFLD. SPARC has potential as preventive or therapeutic target in NAFLD patients.Guillermo MazzoliniCatalina AtorrasagastiAgostina OnoratoEstanislao PeixotoMartin SchlattjanJan-Peter SowaSvenja SydorGuido GerkenAli CanbayNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Guillermo Mazzolini Catalina Atorrasagasti Agostina Onorato Estanislao Peixoto Martin Schlattjan Jan-Peter Sowa Svenja Sydor Guido Gerken Ali Canbay SPARC expression is associated with hepatic injury in rodents and humans with non-alcoholic fatty liver disease
description	Abstract Mechanisms that control progression from simple steatosis to steato-hepatitis and fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) are unknown. SPARC, a secreted matricellular protein, is over-expressed in the liver under chronic injury. Contribution of SPARC accumulation to disease severity is largely unknown in NAFLD. We assessed the hypothesis that SPARC is increased in livers with more necrosis and inflammation and could be associated with more fibrosis. qrt-PCR, immunohistochemistry, and ELISA were employed to localize and quantify changes in SPARC in 62 morbidly obese patients with NAFLD/NASH and in a mouse model of diet-induced-NASH. Results were correlated with the severity of NAFLD/NASH. In obese patients 2 subgroups were identified with either high SPARC expression (n = 16) or low SPARC expression (n = 46) in the liver, with a cutoff of 1.2 fold expression. High expression of SPARC paralleled hepatocellular damage and increased mRNA expression of pro-fibrogenic factors in the liver. In line with these findings, in the NASH animal model SPARC knockout mice were protected from inflammatory injury, and showed less inflammation and fibrosis. Hepatic SPARC expression is associated with liver injury and fibrogenic processes in NAFLD. SPARC has potential as preventive or therapeutic target in NAFLD patients.
format	article
author	Guillermo Mazzolini Catalina Atorrasagasti Agostina Onorato Estanislao Peixoto Martin Schlattjan Jan-Peter Sowa Svenja Sydor Guido Gerken Ali Canbay
author_facet	Guillermo Mazzolini Catalina Atorrasagasti Agostina Onorato Estanislao Peixoto Martin Schlattjan Jan-Peter Sowa Svenja Sydor Guido Gerken Ali Canbay
author_sort	Guillermo Mazzolini
title	SPARC expression is associated with hepatic injury in rodents and humans with non-alcoholic fatty liver disease
title_short	SPARC expression is associated with hepatic injury in rodents and humans with non-alcoholic fatty liver disease
title_full	SPARC expression is associated with hepatic injury in rodents and humans with non-alcoholic fatty liver disease
title_fullStr	SPARC expression is associated with hepatic injury in rodents and humans with non-alcoholic fatty liver disease
title_full_unstemmed	SPARC expression is associated with hepatic injury in rodents and humans with non-alcoholic fatty liver disease
title_sort	sparc expression is associated with hepatic injury in rodents and humans with non-alcoholic fatty liver disease
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/1c427a079f5b42e8bf090c1de65c88de
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SPARC expression is associated with hepatic injury in rodents and humans with non-alcoholic fatty liver disease

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