Expression of liver regeneration-associated protein ALR (Augmenter of Liver Regneration) is diminished by IL-1β

The liver regeneration-associated protein ALR (Augmenter of Liver Regeneration) was shown to exhibit anti-apoptotic, anti-oxidative and autophagic properties. Increased ALR levels have a beneficial impact on liver regeneration, but in chronic liver injury such as cholestasis and NAFLD (non-alcoholic fatty liver disease) expression of ALR is diminished. While several factors are known to induce ALR expression, little is known about its negative regulation. Preliminary results demonstrated that interleukin-1β (IL-1β), e. g. secreted by Kupffer cells in cholestasis, can induce ALR promoter activity. Therefore, we aimed to investigate the regulation of ALR expression by IL-1β. HepG2 and Huh-7 cells were treated with different concentrations of IL-1β and qRT-PCR as well as western-blots were performed. IL-1β treatment reduced ALR mRNA and protein expression in a time- and dose-dependent manner in both cell lines. Expression of hepcidin served as a positive control. Furthermore we analyzed potential transcription factors (TFs) mediating the effect of IL-1β on ALR expression. We found reduced mRNA expression of SP1, a known inducer of ALR, upon IL-1β treatment. In addition Egr-1, another ALR-inducing TF, was hampered to activate ALR expression after IL-1β treatment. Ongoing work elucidates a potential impact of AP1, a TF previously shown to bind onto the ALR promotor repressing its activity. Additionally, expression of HNF4α, a TF known to induce ALR expression, may be reduced by IL-1β and will therefore be analyzed. In conclusion, insights into the regulation of ALR might result in therapeutic strategies to boost its expression and increase its hepatoprotective properties.

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Artikel online veröffentlicht:
26. Januar 2022