Tak, Eunyoung and Ridyard, Douglas and Badulak, Alexander and Giebler, Antasia and Shabeka, Uladzimir and Werner, Tilmann and Clambey, Eric and Moldovan, Radu and Zimmerman, Michael A. and Eltzschig, Holger K. and Grenz, Almut (2013) Protective role for netrin-1 during diabetic nephropathy. JOURNAL OF MOLECULAR MEDICINE-JMM, 91 (9). pp. 1071-1080. ISSN 0946-2716, 1432-1440
Full text not available from this repository. (Request a copy)Abstract
Recent studies implicate neuronal guidance molecules in the orchestration of inflammatory events. For example, previous studies demonstrate a functional role for netrin-1 in attenuating acute kidney injury. Here, we hypothesized a kidney-protective role for netrin-1 during chronic kidney disease, such as occurs during diabetic nephropathy. To study the role of netrin-1 during diabetic nephropathy, we induced diabetes in mice at the age of 8 weeks by streptocotozin (STZ) treatment. Sixteen weeks after STZ treatment, we examined the kidneys. Initial studies in wild-type mice demonstrated robust induction of renal, urinary, and plasma netrin-1 protein levels during diabetic nephropathy. Subsequent genetic studies in mice with partial netrin-1 deficiency (Ntrn1 (+/-) mice) revealed a more severe degree of diabetic nephropathy, including more severe loss of kidney function (albuminuria, glomerular filtration rate, histology). We subsequently performed pharmacologic studies with recombinant netrin-1 treatment given continuously via osmotic pump. Indeed, netrin-1 treatment was associated with attenuated albuminuria and improved histologic scores for diabetic nephropathy compared to controls. Consistent with previous studies implicating purinergic signaling in netrin-1-elicited tissue protection, mice deficient in the Adora2b adenosine receptor were not protected. Taken together, these studies demonstrate a functional role for endogenous netrin-1 in attenuating diabetic kidney disease.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INDUCIBLE FACTOR-I; EXTRACELLULAR ADENOSINE; ECTO-5'-NUCLEOTIDASE CD73; NUCLEOTIDE PHOSPHOHYDROLYSIS; INTESTINAL ISCHEMIA; DEPENDENT INDUCTION; HYPOXIA; INFLAMMATION; GUIDANCE; RECEPTOR; Diabetes; Nephropathy; Netrin-1; Inflammation; Vascular injury; Hypoxia |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Anästhesiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Apr 2020 12:05 |
| Last Modified: | 01 Apr 2020 12:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/16125 |
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