Effect of lentiviral delivery of a chimeric Transforming Growth Factor beta type II receptor against liver fibrosis in rats

ANABEL LA COLLA; MARCELA SOLEDAD BERTOLIO; STELLA MARIS ECHARTE; SABRINA EDITH CAMPISANO; RICARDO A. DEWEY; ANDREA NANCY CHISARI

Congreso; LXII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2017

Sociedad Argentina de Investigación Clínica (SAIC)

Liver brosis is a hallmark feature of chronic liver diseases, which affects millions of patients worldwide, and leads to liver failure. Current therapeutic options for these patients are limited. It is well established that transforming growth factor beta (TGF-β) promotes liver brosis. Thus, the development of therapeutic agents with a signi cant potential to achieve a speci c and long-lasting block of TGF-b action in vivo, is of clinical relevance. The aim of this work was to study, in a carbon tetrachloride (CCl4)-induced liver bro- sis rat model, the effect of lentiviral-mediated overexpression of a chimeric human soluble TGF-b type II receptor ectodomain fused to the Fc portion of human IgG (TGFBR2/Fc). We compared three experimental groups: vehicle, CCl4, and CCl4 previous intrahepatic administration of a lentiviral vector encoding TGFBR2/Fc (Lv-TGF- BR2/Fc). In this way, we observed partial recovery of body weight in rats treated with CCl4 + Lv-TGFBR2/Fc compared to CCl4 group. In addition, gross appearance of livers of Lv-TGFBR2/Fc + CCl4 group reversed the irregular shape and shrinkage observed in CCl4 group. Moreover, injection of Lv-TGFBR2/Fc diminished CCl4-induced liver enzymes augmentation, indicative of liver injury recovery. Histolog- ical analysis of liver sections revealed that Lv-TGFBR2/Fc signi - cantly reduced the deposition of collagen bers induced by CCl4 as well as practically restored liver architecture. These results sug- gest that lentiviral delivery of TGFBR2/Fc exerts a protective effect against liver brosis induced by CCl4 in rats.