Extracellular histones stimulate collagen expression <i>in vitro</i> and promote liver fibrogenesis in a mouse model <i>via</i> the TLR4-MyD88 signaling pathway
Zhi Wang, Zhenxing Cheng, Simon T. Abrams, Zi-Qi Lin, E D Yates, Qian Yu, Weiping Yu, Pingsheng Chen, Cheng‐Hock Toh, Guozheng Wang
Abstract
BACKGROUND: Liver fibrosis progressing to liver cirrhosis and hepatic carcinoma is very common and causes more than one million deaths annually. Fibrosis develops from recurrent liver injury but the molecular mechanisms are not fully understood. Recently, the TLR4-MyD88 signaling pathway has been reported to contribute to fibrosis. Extracellular histones are ligands of TLR4 but their roles in liver fibrosis have not been investigated. AIM: To investigate the roles and potential mechanisms of extracellular histones in liver fibrosis. METHODS: -induced liver fibrosis model was generated in male 6-week-old ICR mice and in TLR4 or MyD88 knockout and parental mice. Circulating histones were detected and the effect of NAHP was evaluated. RESULTS: -induced liver fibrosis. The levels of liver fibrosis were indeed significantly reduced in knockout mice compared to wild type parental mice. CONCLUSION: the TLR4-MyD88 signaling pathway and NAHP has therapeutic potential by detoxifying extracellular histones.