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      1. Author :
        Nakagawa, Naoki; Barron, Luke; Gomez, Ivan G.; Johnson, Bryce G.; Roach, Allie M.; Kameoka, Sei; Jack, Richard M.; Lupher, Mark L.; Gharib, Sina A.; Duffield, Jeremy S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        N/A
      5. Publication :
        JCI Insight
      6. Products :
      7. Volume :
        1
      8. Issue :
        20
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Operetta CLS high-content analysis system; HCS; high-content
      12. 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.
      13. URL :
        https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5135274/
      14. Call Number :
        PKI @ Kathryn.Cook @
      15. Serial :
        23022
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