2016 Fiscal Year Final Research Report
Investigation of the mechanism underlying urinary excretion of megalin, a novel biomarker of diabetic kidney disease
| Project/Area Number |
26860630
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Kidney internal medicine
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| Research Institution | Niigata University |
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Principal Investigator |
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| Research Collaborator |
DE Shankhajit
KUWAHARA Shoji (70645209)
KABASAWA Hideyuki (20794639)
SAITO Akihiko (80293207)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | 糖尿病性腎症 / バイオマーカー / メガリン / 近位尿細管 / エクソソーム |
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| Outline of Final Research Achievements |
I studied the mechanism underlying urinary excretion of megalin, a multiligand endocytic receptor in the proximal tubules, in diabetic kidney disease (DKD). Urinary extracellular vesicle (UEV) excretion and full-length megalin (C-megalin) content in UEVs or in their exosomal fraction increased along with the progression of the albuminuric stages in patients with type 2 diabetes mellitus (T2DM). C-megalin excretion from cultured immortalized rat proximal tubule cells via extracellular vesicles was increased via lysosomal dysfunction in association with megalin-mediated cellular uptake of advanced glycation endproducts, which is significantly blocked by an exosome-specific inhibitor, GW4869. In a high-fat diet-induced, megalin-mediated DKD model in mice, urinary C-megalin excretion also increased via UEVs. Collectively, exocytosis-mediated urinary C-megalin excretion is linked with the megalin-mediated mechanism underlying the development and progression of DKD in T2DM.
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| Free Research Field |
医歯学系
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