THE ABSENCE OF SPARC (SECRETED PROTEIN ACIDIC AND RICH IN CYSTEINE) ATTENUATES LIVER INFLAMMATION AND FIBROSIS IN NON-ALCOHOLIC STEATOHEPATITIS MICE MODELS

ONORATO A; ATORRASAGASTI C; PINEDA F; RODRIGUEZ M; FIORE E; MALVICINI M; MAZZOLINI G

Buenos Aires Argentina

Congreso; LXII REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA; 2017

Non-alcoholic fatty liver (NAFLD) consists of fat accumulation inhepatocytes. It encompasses a set of clinical conditions rangingfrom fatty liver, hepatocyte damage and inflammation (steatohepatitisor NASH) and its subsequent complications: liver fibrosis, cirrhosisand hepatocellular carcinoma. SPARC is a matricellular proteinassociated with inflammatory processes, tissue remodeling, regulationof fibrillar collagen deposits, among other biological functions.The aim of this project was to study the role of SPARC in thecontext of two NASH models: 1) the streptozotocin-induced NASHmodel (STAM); 2) and the diet-induced obesity (DIO) model. ForSTAM model, 2 days old SPARC-/- and SPARC+/+ mice were subcutaneousinjected with 200 mg streptozotocin (SZT) and fed withhigh fat (HF) or control (LF) diet since weaning for 8 weeks. For DIOmodel, SPARC-/- and SPARC+/+ mice were fed for 20 weeks with HF.SPARC and pro-inflammatory cytokines expression were assessedby qPCR. The degree of NASH was measured using the NAS score;and fibrosis was assessed by picrosirius red staining. Triglycerides,cholesterol and serum transaminases were also measured.Liver SPARC expression was increased in HF-fed mice in bothexperimental models. In the STAM model weight curves demonstratedthat SPARC+/+ and SPARC-/- mice, either LF or HF, increasedtheir weight equally; in contrast, DIO model shows weight differencebetween LF and HF fed-mice. HF-fed SPARC-/- mice in STAM modeldeveloped less fibrosis, as well as HF-fed SPARC-/- mice fromDIO model. According to NAS score, HF-fed mice from STAM modeldeveloped NASH after 8 weeks, whereas in DIO model only HFfedSPARC-/- mice develop incipient NASH. Inflammatory cytokinesexpression were increased in HF-fed SPARC+/+ mice compared toSPARC-/- mice from both experimental models.We present novel evidences that demonstrate a role for SPARC inthe development of NASH. SPARC could play a key role as a targetfor prevention of NASH progression.