Interleukin-11 signaling plays limited roles for liver fibrosis in a mouse model of metabolic dysfunction-associated steatohepatitis

Abstract

Liver fibrosis, an abnormal accumulation of collagen fibers in the liver, is caused due to several chronic liver diseases including viral hepatitis, alcoholic steatohepatitis, and metabolic dysfunction-associated steatohepatitis. Among the various symptoms of chronic hepatitis, liver fibrosis is the most crucial factor in determining patient prognosis. Extensive liver fibrosis leads to cirrhosis and liver cancer and shortens the lifespans of patients. However, no drug is currently approved for the treatment of liver fibrosis. Therefore, the identification of molecular mechanisms and druggable targets of liver fibrosis is urgently needed. Interleukin-11 is a member of the interleukin-6 family of inflammatory cytokines that is involved in multiple processes of inflammation and tissue repair. Recent reports also suggest the pro-fibrogenic function of interleukin-11 in various organs. In this study, we examined the fibrogenic potential of interleukin-11 in the liver using a choline-deficient, amino acid-defined high-fat diet, a mouse model of metabolic dysfunction-associated steatohepatitis that rapidly develops liver fibrosis. Although interleukin-11 was specifically upregulated in the liver in this pathological model, the loss of interleukin-11 signaling played minor roles in liver injury, inflammation, fibrosis, and signal transduction pathways. Our results indicate that the pro-fibrogenic function of interleukin-11 may vary among organs and disease etiologies.