Three-protein combination eased chronic liver disease in rats

In an experiment in male Wistar rats, researchers tested three gene-regulating proteins—Oct4, Sox2 and Klf4—and a version that also included c-Myc, another such protein. They delivered the genes in a single dose of a virus and switched them on intermittently with doxycycline, an antibiotic, once a week. Rats had restricted liver blood flow or metabolic dysfunction-associated steatohepatitis, a disease involving liver fat and inflammation. Some rats with the latter disease also had cirrhosis, advanced liver scarring.

Both combinations reduced damage after restricted blood flow. Only the three-protein combination improved chronic liver disease, reducing tissue injury and scarring and increasing survival. The four-protein version offered no benefit in either chronic model. In rats with the metabolic disease but no cirrhosis, it worsened liver injury and scarring, induced tumours and reduced survival.