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 interferoncrucial
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.