Eggshell Membrane Ameliorates Hepatic Fibrogenesis in Human C3A Cells and Rats Through Changes in PPARγ-Endothelin 1 Signaling

Our previous nutrigenomic findings indicate that eggshell membrane (ESM) may prevent liver fibrosis. Here we investigated the effects and mechanisms underlying ESM intervention against liver injury by using DNA microarray analysis and comparative proteomics. In vitro hydrolyzed ESM attenuated the TGFβ1-induced procollagen production of human hepatocyte C3A cells and inhibited the expression of Endothelin 1 (EDN1) and its two receptors, and extracellular matrix components. In vivo male Wistar rats were allocated into a normal control group, a CCl4 group (hypodermic injection of 50% CCl4 2×/wk) and an ESM group (20 g ESM/kg diet with CCl4 injection) for 7 wks. Dietary ESM ameliorated the elevated activity of ALT/AST, oxidative stress and collagen accumulation in liver, accompanied by the down-regulated expression of Edn1 signaling and notable profibrogenic genes and growth factors as well as peroxisome proliferator-activated receptor gamma (PPARγ). Concomitantly, the decreased expressions of Galectin-1 and Desmin protein in the ESM group indicated the deactivation of hepatic stellate cells (HSCs). Through a multifaceted integrated omics approach, we have demonstrated that ESM can exert an antifibrotic effect by suppressing oxidative stress and promoting collagen degradation by inhibiting HSCs' transformation, potentially via a novel modulation of the PPARγ-Endothelin 1 interaction signaling pathway.