Soluble Fn14 Is Detected and Elevated in Mouse and Human Kidney Disease
| Autor: | Shawn P. O'Neil, Gabriela Campanholle, Eva E. Nagiec, Bruce L. Homer, Lih-Ling Lin, Hendrik Neubert, Karrie A. Brenneman, Ju Wang, Margaret Fleming, Steven Evans, Riyez Karim, Yutian Zhan, Priya S. Chockalingam, Nicholas Pullen, M Nusrat Sharif, Jameel Syed |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male B Vitamins Physiology Protein Expression Lupus nephritis lcsh:Medicine Urine Kidney Receptors Tumor Necrosis Factor Diabetic nephropathy Mice Tandem Mass Spectrometry Medicine and Health Sciences lcsh:Science Cytokine TWEAK Multidisciplinary Proteinuria Nephritis Organic Compounds Acute kidney injury Animal Models Vitamins Acute Kidney Injury Lupus Nephritis Up-Regulation Body Fluids Chemistry medicine.anatomical_structure TWEAK Receptor Nephrology Reperfusion Injury Physical Sciences Kidney Diseases medicine.symptom Anatomy Research Article Adult Mouse Models Research and Analysis Methods 03 medical and health sciences Folic Acid Model Organisms medicine Gene Expression and Vector Techniques Animals Humans Animal Models of Disease Molecular Biology Techniques Immunohistochemistry Techniques Molecular Biology Molecular Biology Assays and Analysis Techniques 030102 biochemistry & molecular biology business.industry Organic Chemistry lcsh:R Chemical Compounds Kidney metabolism Biology and Life Sciences Kidneys Renal System medicine.disease Histochemistry and Cytochemistry Techniques Disease Models Animal 030104 developmental biology Solubility Immunology Immunologic Techniques Animal Studies lcsh:Q business Kidney disease Chromatography Liquid |
| Zdroj: | PLoS ONE, Vol 11, Iss 5, p e0155368 (2016) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | 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: | OpenAIRE |
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