Small leucine-rich proteoglycans in kidney disease

Research over the past 2 decades provides ample evidence that small leucine-rich proteoglycans (SLRPs; such as decorin, biglycan, fibromodulin, and lumican) of the extracellular matrix are deeply involved in the regulation of inflammatory and fibrotic renal disorders. Initial efforts in SLRP research focused on the interaction between decorin and TGF-β because it had been unequivocally demonstrated that decorin treatment exerts beneficial effects in fibrotic disorders involving TGF-β overproduction in the kidney. This was followed by a paradigm shift in our understanding of SLRP biology, with new evidence showing that in addition to their role as structural matrix components, soluble SLRPs also act as signaling molecules regulating various complex biologic processes in a molecule- and cell-specific manner. With the identification of SLRP-derived endogenous ligands of Toll-like receptors, the general question regarding the mechanisms of SLRP-derived signaling in pathogen-dependent and independent renal inflammation arose. This led to the fascinating concept of SLRPs as autonomous triggers of sterile renal inflammation in response to renal stress or injury. This review focuses on the key biologic roles of SLRPs in the normal and diseased kidney with special emphasis on newly described signaling events triggered by these proteoglycans.