A Combination of Pirfenidone and Inhibition of TGF-β Mitigates Cystic Echinococcosis–Associated Hepatic Injury

Abstract Background & Aims: TGF-β not only inhibits the function of NK cells, but also promotes liver fibrosis. It is unclear whether the inhibition of TGF-β signaling pathway could relieve the CE-related liver fibrosis.Methods: By using the model of CE infected mouse liver, the effect of the infection of CE exerted on NK cells was identified. In vivo, SB525334 and Pirfenidone were applied to intervene the TGF-β signaling pathway.Results: During the infection of Echinococcus granulosus, the inhibitory receptors on the surface of NK cells increased, while the activated receptors decreased. TGF-β1 secretion was increased in liver tissues and mainly derived from macrophages. At the same time, the combination of drugs could also reduce the expression of TGF-β1 signaling pathway-related proteins and collagen. For the secretion of TGF-β1, only the pirfenidone group had an depressing effect. In addition, the combination of drugs can reduce liver cell damage and restore liver function.Conclusions: During the infection the of Echinococcus granulosus, the dysfunction of NK cells may be caused by increased secretion of TGF-β1 from macrophages. Echinococcus granulosus infection was a process of occupying lesions. This persistent pressure was accompanied by senescent hepatocytes. Senescent hepatocytes induced the secretion of TGF-β1 derived from macrophages, and promoted the activation of hepatic stellate cells and accelerated Echinococcus granulosus-associated liver fibrosis. By combining pirfenidone and SB525334, liver function, senescent hepatocytes, fibrosis associated with Echinococcus granulosus infection could be alleviated. Moreover, the functional status of NK cells also received partially amelioration. In summary, our work offered an experimental basis for clinical treatment.