Liver fibrosis is a wound-healing process of liver featured by the activation of hepatic stellate cells (HSCs) and the deposition of extra cellular matrix (ECM). Accumulating facts have suggested that interleukin (IL) 26 is involved in the pathogenesis of liver fibrosis by the modulation of HSCs. However, the biological roles of IL-26 in liver fibrosis are still unclear. The present study aimed to determine the effect and mechanism of IL-26 on the proliferation and activation of HSCs in vitro. By cell counting kit (CCK)-8 assay, we observed that IL-26 significantly promoted the proliferation of HSCs by increasing S phase and decreasing G0/G1 phase. Annexin V-FITC/PI double staining showed that IL-26 could suppress the apoptosis of HSCs by inhibition of caspase 3 (CASP3) and Bcl-2 associated X protein (BAX). Furthermore, quantitative real-time PCR (qRT-PCR) assay and western blotting analysis revealed that IL-26 exacerbated the degree of hepatic fibrosis, which was associated with the upregulation of the mRNA levels and protein concentrations of IL-6, IL-10, tumor necrosis factor (TNF)-α, matrix metallopeptidase (MMP)-9, and α-smooth muscle act in (SMA). Mechanistically, western blotting analysis showed that IL-26 upregulated the protein expression levels of transforming growth factor (TGF)-β1 and SMAD family member 2 (Smad2) in HSCs. In summary, the data demonstrated a key role of IL-26 on the proliferation and activation of HSCs in liver fibrosis and the underlying mechanism might be related to the TGF-β1/Smad2 signaling pathway. The finding will provide a proof that targeting IL-26 may be developed as therapeutics for liver fibrosis.
Keywords: IL-26; Liver fibrosis; TGF-β1/Smad2; activation; proliferation.
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