Role of humoral factors in the development and progression of metabolic syndrome-related kidney diseases
Project/Area Number |
23591191
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Kidney internal medicine
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Research Institution | Kyoto University |
Principal Investigator |
MUKOYAMA Masashi 京都大学, 医学(系)研究科(研究院), 准教授 (40270558)
|
Co-Investigator(Renkei-kenkyūsha) |
MORI Kiyoshi 京都大学, 医学研究科, 特定准教授 (60343232)
|
Project Period (FY) |
2011 – 2013
|
Project Status |
Completed (Fiscal Year 2013)
|
Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | 腎臓学 / 内分泌学 / メタボリック症候群 / Na利尿ペプチド / アルドステロン / 糖尿病性腎症 / 自然炎症 / ノックアウトマウス / ナトリウム利尿ペプチド / 肥満関連腎症 / toll-like receptor 4 |
Research Abstract |
Metabolic syndrome (MetS) represents impaired regulation of humoral or endocrine factors, such as the enhanced renin-angiotensin-aldosterone system. We investigated roles of humoral factors in MetS-associated renal injury. The natriuretic peptide (ANP and BNP) receptor GC-A is abundantly expressed in renal tubules, but its role in glomerular injury is unknown. When GC-A knockout mice were subjected to aldosterone and high salt, massive proteinuria with marked podocyte injury was observed, which was alleviated with an ARB, antioxidant, or p38 MAPK inhibitor, suggesting their therapeutic potential. In mouse models of diabetes with dyslipidemia, we found that TLR4 and its ligand MRP8, factors associated with homeostatic inflammation, were markedly upregulated together with worsening of nephropathy. Renal injury was significantly alleviated in TLR4-deficient mice. Expression of MRP8 was also enhanced in advanced human diabetic nephropathy, suggesting its role as a prognostic marker.
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Report
(4 results)
Research Products
(39 results)
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[Journal Article] Macrophage-mediated glucolipotoxicity via myeloid-related protein 8/toll-like receptor 4 signaling in diabetic nephropathy2014
Author(s)
Kuwabara, T., Mori, K., Mukoyama, M., Kasahara, M., Yokoi, H., Nakao, K.
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Journal Title
Clinical and Experimental Nephrology
Volume: impress
Issue: 4
Pages: 584-592
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Predictive significance of kidney myeloid-related protein 8 expression in patients with obesity- or type 2 diabetes-associated kidney diseases2014
Author(s)
Kuwabara T, Mori K, Kasahara M, Yokoi H, Imamaki H, Ishii A, Koga K, Sugawara A, Yasuno S, Ueshima K, Morikawa T, Konishi Y, Imanishi M, Nishiyama A, Nakao K, Mukoyama M
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Journal Title
PloS One
Volume: 9
Issue: 2
Pages: e88942-e88942
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Peritoneal fibrosis and high transport are induced in mildly pre-injured peritoneum by 3,4-dideoxyglucosone-3-ene in mice2013
Author(s)
Yokoi, H., Kasahara, M., Mori, K., Kuwabara, T., Toda, N., Yamada, R., Namoto, S., Yamamoto, T., Seki, N., Souma, N., Yamaguchi, T., Sugawara, A., Mukoyama, M., Nakao, K.
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Journal Title
Peritoneal Dialysis International
Volume: 33(2)
Issue: 2
Pages: 143-154
DOI
Related Report
Peer Reviewed
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[Journal Article] Exacerbation of diabetic nephropathy by hyperlipidaemia is mediated by Toll-like receptor 4 in mice2012
Author(s)
Kuwabara T, Mori K, Mukoyama M, Kasahara M, Yokoi H, Saito Y, Ogawa Y, Imamaki H, Kawanishi T, Ishii A, Koga K, Mori KP, Kato Y, Sugawara A, Nakao K
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Journal Title
Diabetologia
Volume: 55:2256-2266
Issue: 8
Pages: 2256-2266
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Natriuretic peptide receptor guanylyl cyclase-A protects podocytes from aldosterone-induced glomerular injury2012
Author(s)
Ogawa Y, Mukoyama M, Yokoi H, Kasahara M, Mori K, Kato Y, Kuwabara T, Imamaki H, Kawanishi T, Koga K, Ishii A, Tokudome T, Kishimoto I, Sugawara A, Nakao K
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Journal Title
J Am Soc Nephrol
Volume: 23:1198-1209
Issue: 7
Pages: 1198-1209
DOI
Related Report
Peer Reviewed
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[Journal Article] Japanese-Western Consensus Meeting on Biomarkers2011
Author(s)
Maisel AS, Nakao K, Ponikowski P, Peacock WF, Yoshimura M, Suzuki T, Tsutamoto T, Filippatos GS, Saito Y, Seino Y, Minamino N, Hirata Y, Mukoyama M, Nishikimi T, Nagai R
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Journal Title
International Heart Journal
Volume: 52
Issue: 5
Pages: 253-265
DOI
NAID
ISSN
1349-2365, 1349-3299
Related Report
Peer Reviewed
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