| Project/Area Number |
22790821
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Neurology
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| Research Institution | Yamaguchi University |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 血液神経関門 / 後期糖化反応生成物 / 糖尿病性末梢神経障害 / 糖尿病性細小血管障害 / ペリサイト / 末梢神経神経内膜内血管内皮細胞 |
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| Research Abstract |
The breakdown of the blood. nerve barrier(BNB) is considered to be a key step in diabetic neuropathy. Although basement membrane hypertrophy and breakdown of the BNB are characteristic features of diabetic neuropathy, the underlying pathogenesis remains unclear. The purpose of the present study was to identify the possible mechanisms responsible for inducing the hypertrophy of basement membrane and the disruption of the BNB after exposure to AGEs using our newly established human peripheral nerve microvascular endothelial cell(PnMEC) and pericyte cell lines. AGEs reduced the production of claudin-5 in PnMECs by increasing autocrine signalling through vascular endothelial growth factor(VEGF) secreted by the PnMECs themselves. Furthermore, AGEs increased the amount of fibronectin, collagen type IV and TIMP-1 in pericytes through a similar upregulation of autocrine VEGF and transforming growth factor(TGF)-released by pericytes. These results indicate that pericytes may be the main regulators of the basement membrane at the BNB. AGEs induce basement membrane hypertrophy and disrupt the BNB by increasing autocrine VEGF and TGF-signalling by pericytes under diabetic conditions.
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