Abstract
Macrophage stimulating protein (MSP) was discovered as a serum protein affecting macrophage motility, and found to be similar with a hepatocyte growth factor (HGF)-family molecule, HGF-liked protein (HLP). MSP/HLP has 45% sequence similarity with HGF. Inactive pro-MSP is synthesized by hepatocytes and released into the circulating blood, and its activation is regulated in disease pathologies such as in inflammation and cancer progression. Through binding to the RON receptor, MSP acts in innate- immune responses and anti- inflammation, and prevents the induction of iNOS, COX-2, and PGE2 in response to endotoxin and interferon-
crucial regulator of inflammation in multiple animal disease models of the liver, kidney, lung, gut and other organs. Also, MSP suppresses glucose production and negatively regulates the expression of gluconeogenic enzymes. HGF-Met and MSP-Ron signaling have analogous functions. In future, MSP/RON signaling becomes a new important drug target, especially for excess inflammation, and the inhibition of Ron inhibitors is expected for cancer therapy.