Extended Data Fig. 1: GPNMB is a top upregulated gene in MASH and Gpnmb ablation ameliorates steatosis.
(a and b) RNA-seq analysis of differentially expressed hepatic genes from WT mice fed a normal chow diet (ND), a high-fat/high-cholesterol (HFHC) diet, or an AMLN diet (GSE119340) for 4 months. (c) Hepatic GPNMB expression (log2) in healthy, MASLD, and MASH patients (GSE162694, health n = 31, MASLD n = 65, MASH n = 47; GSE135251, health n = 10, MASLD n = 51, MASH n = 155; GSE89632, health n = 24, MASLD n = 20, MASH n = 19; GSE274114, health n = 9, MASH n = 10; GSE240729, MASLD n = 26, MASH n = 41). The box plots show the interquartile range (IQR; Q1-Q3) (box limits), the median (center line), and the minimum (Q1-1.5×IQR) and maximum (Q3 + 1.5×IQR) values (whiskers). P values were calculated using unpaired two-tailed Student’s t-tests. (d to j) Eight-week-old male WT and Gpnmb−/− mice were fed a HFD for 4 months. BW (d), cumulative food intake (e), H&E and Oil Red O staining, α-SMA immunostaining, and Sirius Red staining, scale bar, 200 μm; representative gross appearance of livers and eWAT, scale bar, 5000 μm (f), histological evaluation of MASLD activity and fibrosis (g), liver TG (h), serum AST and ALT (i), and hepatic expression of inflammatory and fibrogenic genes (j) (WT n = 9, Gpnmb−/− n = 8 mice). Data are presented as mean ± SEM (d, g-j). Unpaired two-tailed Student’s t-test (d, g-j).
