Fig. 4: HGF/EGF mRNA-LNP accelerate restoration of liver function during recovery from CDE-induced chronic liver injury.

a Injury scheme timeline: mice were fed CDD choline deficient diet for 1 week followed by three weeks of CDD diet supplemented with 0.1% ethionine (CDE). The CDE diet was then replaced with choline-sufficient diet. Mice were injected with either controls Poly(C) RNA or Luc mRNA-LNP, or HGF(H) and EGF(E) single or combined (H/E) mRNA-LNP at the end of the CDE diet (T0), followed by another injection 4 days into recovery (T4). b Bright-field images at ×100 magnification of Oil Red O staining showing lipid accumulation in hepatocytes at T2 and T8 in mice injected with either Poly(C) RNA-LNP or H/E mRNA-LNP. Representative images from 3 to 4 mice per group are shown. The scale bar represents 200 μm for all ×100 magnification images. Analyses of total serum cholesterol levels (c) and ALT levels (d) from 3 to 4 mice per group in duplicate or triplicate (n = 8–12) per time point treated with controls Poly(C) RNA-LNP or Luc mRNA-LNP, or single HGF(H), single EGF(E) or the combination H/E mRNA-LNP indicate sharp reversion of steatosis and restoration of basic levels of ALT after H/E mRNA-LNP injections. Data are presented as mean values ± SEM. Dark grey: T0, light grey: control RNA, light blue: single mRNA, dark blue: combined mRNA. P values were calculated by two-sided student’s t test, ***<0.0001, **<0.001, *<0.05, n.s. = not significant. Source data are provided as a Source Data file.