Advances in Anti-metabolic Disease Treatments Targeting CD47

Abstract

Metabolic disorders include a cluster of conditions that result from hyperglycemia, hyperlipidemia, insulin resistance, obesity, and hepatic steatosis, which cause the dysfunction of immune cells and innate cells, such as macrophages, natural killer cells, vascular endothelial cells, hepatocytes, and human kidney tubular epithelial cells. Besides targeting the derangements in lipid metabolism, therapeutic modulations to regulate abnormal responses in the immune system and innate cell dysfunctions may prove to be promising strategies in the management of metabolic diseases. In recent years, several targets have been explored for the CD47 molecule (CD47), a glycosylated protein, which was originally reported to transmit an anti-phagocytic signal known as "don't eat me" in the atherosclerotic environment, hindering the efferocytosis of immune cells and promoting arterial plaque accumulation. Subsequently, the role of CD47 has been explored in obesity, fatty liver, and lipotoxic nephropathy, and its utility as a therapeutic target has been investigated using anti-CD47 antibodies or inhibitors of the THBS1/CD47 axis and the CD47/SIRPα signaling pathway. This review summarizes the mechanisms of action of CD47 in different cell types during metabolic diseases and the clinical research progress to date, providing a reference for the comprehensive targeting of CD47 to treat metabolic diseases and the devising of potential improvements to possible side effects.

Keywords: CD47 molecule.; Metabolic disease; atherosclerosis; hepatic steatosis; lipotoxic nephropathy; obesity.