Mzb1 Promotes Progression of Schistosomiasis by Inducing Endoplasmic Reticulum Stress.

Abstract

Despite advances in anthelmintic therapy, there are currently no effective treatments for schistosomiasis-induced liver fibrosis. Previous studies have reported elevated marginal zone B and B1 cell specific protein (MZB1) expression in fibrotic diseases, but its function remains unclear, and its role in schistosomiasis has not been investigated. This study aimed to explore the function and mechanism of MZB1 in Schistosoma japonicum infection. We evaluated the expression of Mzb1 in the liver and spleen of Schistosoma-infected mice using methods such as Western blot, qPCR, and immunohistochemistry. We also employed adeno-associated virus (AAV) to knock down Mzb1 gene expression, assessing the role of Mzb1 in the progression of schistosomiasis and its downstream pathways. Additionally, in vivo experiments were conducted using downstream endoplasmic reticulum stress agonists and inhibitors to evaluate the role of this pathway in the progression of schistosomiasis. Our findings demonstrated that Mzb1 was significantly upregulated in the liver and spleen tissues of infected mice. Knockdown of Mzb1 markedly reduced liver fibrosis and splenomegaly. Mzb1 was predominantly expressed in CD20-positive B cells and was found to activate endoplasmic reticulum (ER) stress. Inhibition of ER stress alleviated liver fibrosis and splenomegaly, while activation of ER stress exacerbated these pathological conditions and reversed the protective effects of Mzb1 knockdown. We identified Mzb1 as a key factor that promotes liver fibrosis and splenomegaly in schistosomiasis through the activation of ER stress. This novel pathogenic mechanism may provide a potential therapeutic target for the treatment of schistosomiasis-induced liver fibrosis.