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

Guillermo Mazzolini, Catalina Atorrasagasti, Agostina Onorato, Estanislao Peixoto, Martin Schlattjan, Jan Peter Sowa, Svenja Sydor, Guido Gerken, Ali Canbay

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


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.

Original languageEnglish (US)
Article number725
JournalScientific reports
Issue number1
StatePublished - Dec 1 2018
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the Deutsche Forschungsgemeinschaft (DFG, grant CA267/14–1 to A.C.), the Wilhelm-Laupitz-Foundation (AC), Austral University (T-13 for GM), Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT) grant PICT 2012/1407 (GM), DAD grant ref 91577391 (to DM), PICT 2014/2666 (CA), and from National Cancer Institute, Argentina (GM).

Publisher Copyright:
© 2018 The Author(s).


Dive into the research topics of 'SPARC expression is associated with hepatic injury in rodents and humans with non-alcoholic fatty liver disease'. Together they form a unique fingerprint.

Cite this