Soluble Fn14 Is Detected and Elevated in Mouse and Human Kidney Disease.

Autor: Sharif MN; Inflammation and Immunology Research Unit, Pfizer Inc., Cambridge, MA, United States of America., Campanholle G; Inflammation and Immunology Research Unit, Pfizer Inc., Cambridge, MA, United States of America., Nagiec EE; Pfizer Worldwide Drug Safety Research and Development, Cambridge, MA, United States America., Wang J; Inflammation and Immunology Research Unit, Pfizer Inc., Cambridge, MA, United States of America., Syed J; Pfizer Worldwide Drug Safety Research and Development, Andover, MA, United States of America., O'Neil SP; Pfizer Worldwide Drug Safety Research and Development, Andover, MA, United States of America., Zhan Y; Pfizer Worldwide Drug Safety Research and Development, Andover, MA, United States of America., Brenneman K; Pfizer Worldwide Drug Safety Research and Development, Andover, MA, United States of America., Homer B; Pfizer Worldwide Drug Safety Research and Development, Andover, MA, United States of America., Neubert H; Department of Pharmacokinetics, Dynamics and Metabolism, Pfizer Inc., Andover, MA, United States of America., Karim R; Global Biological Technology, Pfizer Inc., Cambridge, MA, United States of America., Pullen N; Inflammation and Immunology Research Unit, Pfizer Inc., Cambridge, MA, United States of America., Evans SM; Inflammation and Immunology Research Unit, Pfizer Inc., Cambridge, MA, United States of America., Fleming M; Inflammation and Immunology Research Unit, Pfizer Inc., Cambridge, MA, United States of America., Chockalingam P; Inflammation and Immunology Research Unit, Pfizer Inc., Cambridge, MA, United States of America., Lin LL; Inflammation and Immunology Research Unit, Pfizer Inc., Cambridge, MA, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2016 May 12; Vol. 11 (5), pp. e0155368. Date of Electronic Publication: 2016 May 12 (Print Publication: 2016).
DOI: 10.1371/journal.pone.0155368
Abstrakt: The cytokine TWEAK and its cognate receptor Fn14 are members of the TNF/TNFR superfamily and are upregulated in tissue injury to mediate local tissue responses including inflammation and tissue remodeling. We found that in various models of kidney disease, Fn14 expression (mRNA and protein) is upregulated in the kidney. These models include: lupus nephritis mouse models (Nephrotoxic serum Transfer Nephritis and MRL.Faslpr/lpr), acute kidney injury models (Ischemia reperfusion injury and Folic acid injury), and a ZSF-1 diabetic nephropathy rat model. Fn14 expression levels correlate with disease severity as measured by disease histology. We have also shown for the first time the detection of soluble Fn14 (sFn14) in the urine and serum of mice. Importantly, we found the sFn14 levels are markedly increased in the diseased mice and are correlated with disease biomarkers including proteinuria and MCP-1. We have also detected sFn14 in human plasma and urine. Moreover, sFn14 levels, in urine are significantly increased in DN patients and correlated with proteinuria and MCP-1 levels. Thus our data not only confirm the up-regulation of Fn14/TWEAK pathway in kidney diseases, but also suggest a novel mechanism for its regulation by the generation of sFn14. The correlation of sFn14 levels and disease severity suggest that sFn14 may serve as a potential biomarker for both acute and chronic kidney diseases.
Databáze: MEDLINE
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