The role of sparc (secreted protein acidic and rich in cysteine) in the liver sinusoidal endothelium in an experimental model of acute liver failure.

ATORRASAGASTI C ; PEIXOTO E; MALVICCINI M; FIORE E; BAYO J; GARCIA MG; MAZZOLINI G

Congreso; Reunión Conjunta de Sociedades de Biociencias.; 2017

Acute liver failure (ALF) is characterized by a rapid deterioration of liver function. Liver sinusoidal endothelial cells (LSEC) have a key role during ALF. Different pathological agents can target LSEC, disrupting sinusoidal endothelium and facilitating T-cell migration into liver parenchyma. SPARC is a matricellular protein involved in many processes including cell-cell interaction and adhesion. After injury, SPARC is overexpressed in EC inducing different cellular processes. We have observed that SPARC-/- mice are protected from ALF damage. In this work, we study the role of SPARC in sinusoidal endothelial injury. In an in vivo approach of ALF, SPARC+/+ and SPARC-/- mice were subjected to conA injury and LSEC monolayer morphology was studied by electronic microscopy. LSEC primary cultured from SPARC+/+ and SPARC-/- were used to study the effects of conA in vitro. SPARC expression, cytoskeletal structure, cell morphology and activation were assessed. Microscopic analysis revealed that LSEC monolayer was well preserved and less activated in conA-treated SPARC-/- mice compared to SPARC+/+. SPARC-/- LSEC phenotype and endocytic capacity were conserved. SPARC expression was increased in conA-treated LSEC (7.3±1 vs 1±0.1). In addition, SPARC-/-conA-treated LSEC showed a marked decrease in VCAM-1 expression; cell morphology was more preserved and no alterations in actin cytoskeleton organization in SPARC-/- mice; contrarily, SPARC+/+LSEC showed a clear disturbance in cell appearance and actin filament architecture. Consistently, qPCR analysis showed that SPARC-/-conA-treated LSEC increased their expression of capzb (1.7±0.1 vs 1.2±0.1), a regulator of actin filament dynamics, and decreased tubb2b expression (0.01±0.1 vs 2.4±0.01), a major component of microtubules, compared with SPARC+/+conA-treated LSEC. Our results suggest that SPARC plays an interesting role in LSEC under conA damage. Inhibition of SPARC merits further investigation as a potential therapeutic target.