FEATURED PUBLICATIONS

Fate Tracing Reveals the Pericyte and Not Epithelial Origin of Myofibroblasts in Kidney Fibrosis
Deficient Autophagy Results in Mitochondrial Dysfunction and FSGS
Cellular and Molecular Mechanisms in Kidney Fibrosis
Anti-microRNA-21 Oligonucleotides Prevent Alport Nephropathy Progression by Stimulating Metabolic Pathways
LRP-6 is a Coreceptor for Multiple Fibrogenic Signaling Pathways in Pericytes and Myofibroblasts That are Inhibited by DKK-1
Dicer1 Activity in the Stromal Compartment Regulates Nephron Differentiation and Vascular Patterning During Mammalian Kidney Organogenesis

Lab Publications

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

Icon for American Society for Clinical Investigation Icon for PubMed Central Related Articles

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

JCI Insight. 2016 12 08;1(20):e87446

Authors: Nakagawa N, Barron L, Gomez IG, Johnson BG, Roach AM, Kameoka S, Jack RM, Lupher ML, Gharib SA, Duffield JS

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

PMID: 27942582 [PubMed - indexed for MEDLINE]