From Inflammation to Fibrosis: Novel Insights into the Roles of High Mobility Group Protein Box 1 in Schistosome-Induced Liver Damage

• Published in: Pathogens (Basel) 2022-02, Vol.11 (3), p.289
• Main Authors: Zhong, Haoran, Gui, Xiang, Hou, Ling, Lv, Rongxue, Jin, Yamei
• Format: Article
• Language: English
• Subjects: Advanced glycosylation end products; Animal diseases; Animal models; Binding sites; Cell surface; Complications; Cytokines; Damage; Drug development; Eggs; Fibrosis; Glycosylation; Granuloma; granulomas; hepatic fibrosis; high mobility group protein box 1; High mobility group proteins; HMGB1 protein; Hypertension; Immune response; Immune system; Immunosuppressive agents; Infections; Inflammation; Kinases; Liver; Liver diseases; Malaria; Mammals; Mobility; Morbidity; Parasitic diseases; Phenotypes; Praziquantel; Proteins; Receptors; Review; Schistosomiasis; Signal transduction; Stellate cells; Therapeutic targets; Toll-like receptors; Tropical diseases; Vector-borne diseases
• ISSN: 2076-0817; 2076-0817
• DOI: 10.3390/pathogens11030289

Schistosomiasis is a chronic helminthic disease of both humans and animals and the second most prevalent parasitic disease after malaria. Through a complex migration process, schistosome eggs trapped in the liver can lead to the formation of granulomas and subsequent schistosome-induced liver damage, which results in high mortality and morbidity. Although praziquantel can eliminate mature worms and prevent egg deposition, effective drugs to reverse schistosome-induced liver damage are scarce. High mobility group box 1 (HMGB1) is a multifunctional cytokine contributing to liver injury, inflammation, and immune responses in schistosomiasis by binding to cell-surface Toll-like receptors and receptors for advanced glycation end products. HMGB1 is increased in the serum of patients with schistosomiasis and enables hepatic stellate cells to adopt a proliferative myofibroblast-like phenotype, which is crucial to schistosome-induced granuloma formation. Inhibition of HMGB1 was found to generate protective responses against fibrotic diseases in animal models. Clinically, HMGB1 presents a potential target for treatment of the chronic sequelae of schistosomiasis. Here, the pivotal role of HMGB1 in granuloma formation and schistosome-induced liver damage, as well the potential of HMGB1 as a therapeutic target, are discussed.