Function of C6ORF120 gene in CCL4- induced liver fibrosis in rats

Liver fibrosis is a progressive stage of multiple chronic liver diseases. C6ORF120, a gene with unknown function, has been found to play an important role in autoimmune hepatitis and acute liver injury; however, its function in liver fibrosis remains unexplored. C6ORF120-/- rats were constructed by using TALEN-mediated knockout technology, which causes a depletion of four bases of TTTG at a specific position in the DNA sequence of the C6ORF120 gene, resulting in a shifted mutation. The pro-fibrotic effect of C6ORF120 was observed in wild-type and C6ORF120-/- SD rats (6-8 weeks,180-220g) induced by 8-week intraperitoneal injection with CCL4 (2mg/kg, twice a week). Moreover, we found that the pro-fibrotic effects of C6ORF120 were associated with stellate cell activation and extracellular matrix organization. Milder extracellular matrix organization in C6ORF120-/- rats was associated with less activation of the PI3K/AKT pathway. This provides a possible target for the treatment of liver fibrosis.