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  Circulating fibronectin contributes to mesangial expansion in a murine model of type 1 diabetes

Klemis, V., Ghura, H., Federico, G., Wuerfel, C., Bentmann, A., Gretz, N., et al. (2017). Circulating fibronectin contributes to mesangial expansion in a murine model of type 1 diabetes. Kidney International, 91(6), 1374-1385. doi:10.1016/j.kint.2016.12.006.

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 Creators:
Klemis, Verena1, Author              
Ghura, Hiba1, Author              
Federico, Giuseppina2, Author
Wuerfel, Carina1, Author              
Bentmann, Anke1, Author              
Gretz, Norbert2, Author
Miyazaki, Tatsuhiko2, Author
Groene, Hermann-Joseph2, Author
Nakchband, Inaam A.2, Author
Affiliations:
1Nakchbandi, Inaam / Translational Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565162              
2external, ou_persistent22              

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Free keywords: STRUCTURAL-FUNCTIONAL RELATIONSHIPS; EARLY NATURAL-HISTORY; PROTEIN-KINASE-C; EXTRACELLULAR-MATRIX; IN-VIVO; GLOMERULAR STRUCTURE; PLASMA FIBRONECTIN; HIGH GLUCOSE; MOUSE MODEL; CELLSUrology & Nephrology; circulation; diabetes mellitus; fibronectin; mesangial expansion; nephropathy;
 Abstract: Fibronectin is ubiquitously expressed in the extracellular matrix, and its accumulation in the glomerular mesangium in diabetic nephropathy is associated with deterioration of renal function in these patients. However, the exact role of fibronectin in the pathogenesis of diabetic nephropathy remains unknown. To clarify this, we administered fluorescent-labeled plasma fibronectin to wild-type mice and found it to accumulate in the mesangium. Using liver-specific conditional-knockout mice to decrease circulating fibronectin, we reduced circulating fibronectin by more than 90%. In streptozotocin-induced diabetes of these knockout mice, the pronounced fall in circulating fibronectin resulted in a decrease in mesangial expansion by 25% and a decline in albuminuria by 30% compared to diabetic control mice. Indeed, the amount of fibronectin in the kidney was reduced, as was the total amount of collagen. In vitro experiments confirmed that matrix accumulation of fibronectin was enhanced by increasing fibronectin only, glucose only, or the combination of both. Thus, circulating fibronectin contributes to mesangial expansion and exacerbation of albuminuria in a murine model of type 1 diabetes.

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Language(s): eng - English
 Dates: 2017-01-312017-06
 Publication Status: Published in print
 Pages: 12
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Degree: -

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Title: Kidney International
Source Genre: Journal
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Publ. Info: New York, NY : Elsevier ; International Society of Nephrology
Pages: - Volume / Issue: 91 (6) Sequence Number: - Start / End Page: 1374 - 1385 Identifier: ISSN: 0085-2538
CoNE: https://pure.mpg.de/cone/journals/resource/954927608814_1