Fig. 4: HSC-derived RSPO3 regulates hepatocyte injury, liver regeneration and steatosis.
From: Hepatic stellate cells control liver zonation, size and functions via R-spondin 3
a, Ki-67 and cyclin D1 IHC from Rspo3fl/fl (n = 7) and Rspo3ΔHSC (n = 6) mice subjected to 70% PHx. b–d, The necrosis area (n = 5 (Rspo3fl/fl), n = 6 (Rspo3ΔHSC)), ALT levels (n = 5 (Rspo3fl/fl), n = 6 (Rspo3ΔHSC)) and survival (n = 12 (Rspo3fl/fl), n = 10 (Rspo3ΔHSC)) in Rspo3fl/fl and Rspo3ΔHSC mice treated with APAP (b; 300 mg per kg or 750 mg per kg lethal dose); the necrosis area (n = 3 per group) and ALT levels (n = 7 per group) in Rspo3fl/fl and Rspo3ΔHSC mice treated with CCl4 (c, 0.5 ml kg−1); and the necrosis area (n = 8 per group), ALT levels (n = 8 per group) and survival (n = 14 (Rspo3fl/fl), n = 12 (Rspo3ΔHSC)) in Rspo3fl/fl and Rspo3ΔHSC mice treated with allyl alcohol (d; 60 mg per kg or 75 mg per kg lethal dose). e, Zonal quantification of Ki-67+ cells (n = 7 (Rspo3fl/fl), n = 6 (Rspo3ΔHSC)) and necrosis in APAP (n = 5 (Rspo3fl/fl), n = 6 (Rspo3ΔHSC)), CCl4 (n = 3 per group) and allyl alcohol (n = 8 per group) models in Rspo3fl/fl and Rspo3ΔHSC mice. f, Oil Red O staining and quantification, serum ALT and AST, and qPCR analysis of Aldh2 mRNA in Rspo3fl/fl (n = 11) and Rspo3ΔHSC (n = 9) mice treated with the Lieber–DeCarli diet. g, Oil Red O staining and quantification, the serum ALT and AST (n = 10 (Rspo3fl/fl), n = 11 (Rspo3ΔHSC)), representative images and the tumour number and tumour size in Rspo3fl/fl (n = 8) and Rspo3ΔHSC mice (n = 7) that were treated with CDAA-HFD diet for the indicated times. h, DESI–MS imaging showing triglycerides (TG; 52:3, red) and phosphatidylcholine (PC; 36:5, blue) in Rspo3fl/fl and Rspo3ΔHSC (n = 4 per group) mice as well as a representative for localization of TG 52:3 around pericentral zones marked by GS (green) and quantification of TG 52:3, TG 52:4 and TG 55:8 species. Data are mean ± s.e.m. Each dot represents one biological replicate (a–d and f–h). Scale bars, 100 µm (a–d, f and g), 1 cm (h, left), 1 mm (h, right). P values were calculated using unpaired two-tailed t-tests (a, c and e–h, and b and d (top)) or log-rank tests (b and d (bottom)).
