Serum Amyloid P prevents renal fibrosis

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Congratulations to my colleague at the Brigham, Jeremy Duffield, who made the cover of Science this week for demonstrating human Serum Amyloid P (hSAP) potently inhibits fibrosis in two independent models of renal fibrosis. hSAP is a naturally circulating soluble pattern recognition receptor, and radio-labelled SAP is used clinically to identify sites of amyloid deposition in systemic amyloidosis. In the studies, hSAP was given to mice with either unilateral ureteric obstruction or unilateral ischemia reperfusion mediated kidney injury. In both cases, hSAP potently suppressed fibrotic collagen protein and collagen gene expression in a sustained fashion, preventing the development of interstitial fibrosis. hSAP acts by binding danger molecules at sites of tissue injury, causing the complexes to be cleared by the Fcγ family of receptors on macrophages. This results in suppression of inflammatory and fibrotic gene and protein expression in monocyte-derived cells, via an interleukin-10 dependant mechanism. These findings raise the possibility of using hSAP as a therapy for kidney diseases with a prominent fibrotic component, such as diabetic nephropathy or chronic allograft nephropathy. A recombinant form of human Serum Amyloid P, PRM-151 (rhSAP), is already in phase 1 trials.

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