Abstract | BACKGROUND: METHODS: Proximal tubular epithelium-specific UNC5B knockout mice as well as heterozygous UNC5B knockout mice were used to determine the roles of UNC5B in nephropathy. Diabetes was induced in these tissue-specific knockout, heterozygous and WT mice, and albuminuria was then monitored. RESULTS: WT and heterozygous diabetic mice developed significant albuminuria at 8 weeks after induction of diabetes as compared to buffer-treated control mice. However, albuminuria was significantly more pronounced in mice with proximal tubule specific deletion of UNC5B. Transgenic overexpression of netrin-1 in proximal tubules in the DBA background and administration of recombinant netrin-1 to Ins2Akita mice also significantly reduced diabetes-induced albuminuria and suppressed glomerular and interstitial lesions. CONCLUSION: Our data suggested that netrin-1 signaling in proximal tubular epithelium may play a critical role in the protection of kidney against diabetic kidney disease.
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Authors | Punithavathi Ranganathan, Riyaz Mohamed, Calpurnia Jayakumar, Michael W Brands, Ganesan Ramesh |
Journal | American journal of nephrology
(Am J Nephrol)
Vol. 41
Issue 3
Pg. 220-30
( 2015)
ISSN: 1421-9670 [Electronic] Switzerland |
PMID | 25896231
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | © 2015 S. Karger AG, Basel. |
Chemical References |
- Nerve Growth Factors
- Netrin Receptors
- Ntn1 protein, mouse
- Receptors, Cell Surface
- Tumor Suppressor Proteins
- Netrin-1
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Topics |
- Albuminuria
(blood)
- Animals
- Diabetes Mellitus, Experimental
(metabolism, pathology)
- Diabetic Nephropathies
(metabolism, pathology)
- Disease Models, Animal
- Epithelial Cells
(drug effects, metabolism, pathology)
- Heterozygote
- Kidney Tubules, Proximal
- Mice
- Mice, Knockout
- Nerve Growth Factors
(genetics, metabolism, pharmacology)
- Netrin Receptors
- Netrin-1
- Receptors, Cell Surface
(deficiency, genetics)
- Signal Transduction
(drug effects)
- Treatment Outcome
- Tumor Suppressor Proteins
(genetics, metabolism, pharmacology)
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