https://www.sciencedirect.com/science/article/abs/pii/S0161589024000798
Molecular Immunology, Volume 170, June 2024, Pages 60-75
Mingkang Zhang, Jinru Yang, Yufan Yuan, Yan Zhou, Yazhi Wang, Ruirui Cui, Yimai Maliu, Fen Xu, Xin’an Wu
Highlights
• CCl4 induced the recruitment and activation of MCs leading to hepatic fibrosis.
• Coadministration of SCG or KET stabilized MCs by decreasing the expression of SCF/c-kit.
• Coadministration of SCG or KET attenuated liver fibrosis by inhibiting the TGF-β1/Smad2/3 and HIF-1α/VEGF pathways.
• Coadministration of SCG or KET attenuated liver fibrosis by activating the Nrf2/HO-1 pathway.
Abstract
Liver diseases caused by viral infections, alcoholism, drugs, or chemical poisons are a significant health problem: Liver diseases are a leading contributor to mortality, with approximately 2 million deaths per year worldwide. Liver fibrosis, as a common liver disease characterized by excessive collagen deposition, is associated with high morbidity and mortality, and there is no effective treatment. Numerous studies have shown that the accumulation of mast cells (MCs) in the liver is closely associated with liver injury caused by a variety of factors. This study investigated the relationship between MCs and carbon tetrachloride (CCl4)-induced liver fibrosis in rats and the effects of the MC stabilizers sodium cromoglycate (SGC) and ketotifen (KET) on CCl4-induced liver fibrosis. The results showed that MCs were recruited or activated during CCl4-induced liver fibrosis. Coadministration of SCG or KET alleviated the liver fibrosis by decreasing SCF/c-kit expression, inhibiting the TGF-β1/Smad2/3 pathway, depressing the HIF-1a/VEGF pathway, activating Nrf2/HO-1 pathway, and increasing the hepatic levels of GSH, GSH-Px, and GR, thereby reducing hepatic oxidative stress. Collectively, recruitment or activation of MCs is linked to liver fibrosis and the stabilization of MCs may provide a new approach to the prevention of liver fibrosis.
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