RAGE pathways play an important role in regulation of organ fibrosis

Organ fibrosis is a pathological process of fibroblast activation and excessive deposition of extracellular matrix after persistent tissue injury and therefore is a common endpoint of many organ pathologies. Multiple cellular types and soluble mediators, including chemokines, cytokines and non-peptidic factors, are implicated in fibrogenesis and the remodeling of tissue architecture. The molecular basis of the fibrotic process is complex and consists of closely intertwined signaling networks. Research has strived for a better understanding of these pathological mechanisms to potentially reveal novel therapeutic targets for fibrotic diseases. In light of new knowledge, the receptor for advanced glycation end products (RAGE) emerged as an important candidate for the regulation of a wide variety of cellular functions related to fibrosis, including inflammation, cell proliferation, apoptosis, and angiogenesis. RAGE is a pattern recognition receptor that binds a broad range of ligands such as advanced glycation end products, high mobility group box-1, S-100 calcium-binding protein and amyloid beta protein. Although the link between RAGE and fibrosis has been established, the exact mechanisms need be investigated in further studies. The aim of this review is to collect all available information about the intricate function of RAGE and its signaling cascades in the pathogenesis of fibrotic diseases within different organs. In addition, to the major ligands and signaling pathways, we discuss potential strategies for targeting RAGE in fibrosis. We emphasize the functional links between RAGE, inflammation and fibrosis that may guide further studies and the development of improved therapeutic drugs.