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

MAZZOLINI, GUILLERMO; ATORRASAGASTI, CATALINA; ONORATO, AGOSTINA; PEIXOTO, ESTANISLAO; SCHLATTJAN, MARTIN; SOWA, JAN-PETER; SYDOR, SVENJA; GERKEN, GUIDO; CANBAY, ALI

Scientific Reports

Nature

Año: 2018 vol. 8

Mechanisms that control progression from simple steatosis to steato-hepatitis and fbrosis in patientswith non-alcoholic fatty liver disease (NAFLD) are unknown. SPARC, a secreted matricellular protein, isover-expressed in the liver under chronic injury. Contribution of SPARC accumulation to disease severityis largely unknown in NAFLD. We assessed the hypothesis that SPARC is increased in livers with morenecrosis and infammation and could be associated with more fbrosis. qrt-PCR, immunohistochemistry,and ELISA were employed to localize and quantify changes in SPARC in 62 morbidly obese patients withNAFLD/NASH and in a mouse model of diet-induced-NASH. Results were correlated with the severity ofNAFLD/NASH. In obese patients 2 subgroups were identifed with either high SPARC expression (n=16)or low SPARC expression (n=46) in the liver, with a cutof of 1.2 fold expression. High expression ofSPARC paralleled hepatocellular damage and increased mRNA expression of pro-fbrogenic factors inthe liver. In line with these fndings, in the NASH animal model SPARC knockout mice were protectedfrom infammatory injury, and showed less infammation and fbrosis. Hepatic SPARC expression isassociated with liver injury and fbrogenic processes in NAFLD. SPARC has potential as preventive ortherapeutic target in NAFLD patients