Pentraxin-2 suppresses c-Jun/AP-1 signaling to inhibit progressive fibrotic disease

• DOI: 10.1172/jci.insight.87446
• Publication Date: 2016-12-07T16:00:58Z
• Authors: Naoki Nakagawa; Luke Barron; Ivan G. Gomez; Bryce G. Johnson; Allie M. Roach; Sei Kameoka; Richard M. Jack; Mark L. Lupher; Sina A. Gharib; Jeremy S. Duffield
• Keywords: Mice, Knockout; 0303 health sciences; Mice, 129 Strain; Proto-Oncogene Proteins c-jun; Nephritis, Hereditary; Nerve Tissue Proteins; Macrophage Activation; Kidney; Fibrosis; Monocytes; Recombinant Proteins; 3. Good health; Transcription Factor AP-1; Mice; 03 medical and health sciences; C-Reactive Protein; Animals; Humans; Cells, Cultured; Signal Transduction

Pentraxin-2 (PTX-2), also known as serum amyloid P component (SAP/APCS), is a constitutive, antiinflammatory, innate immune plasma protein whose circulating level decreased in chronic human fibrotic diseases. Here we show that recombinant PTX-2 (rhPTX-2) retards progression of kidney disease Col4a3 mutant mice with Alport syndrome, reducing blood markers failure, enhancing lifespan by 20%, and improving histological signs disease. Exogenously delivered rhPTX-2 was detected macrophages but tubular epithelial cells, where it counteracted macrophage activation cytoprotective for the epithelium. Computational analysis genes regulated identified transcriptional regulator c-Jun along its activator protein–1 (AP-1) binding partners central target function rhPTX-2. Accordingly, attenuates AP-1 activity, reduces expression AP-1–dependent inflammatory both monocytes Our studies therefore identify potential therapy an important inhibitor pathological signaling this setting.