2010 Fiscal Year Final Research Report
Translational research and clinical application of the natriuretic peptide system in the kidney.
| Project/Area Number |
20590956
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Kidney internal medicine
|
|---|
| Research Institution | Kyoto University |
|---|
Principal Investigator |
MUKOYAMA Masashi Kyoto University, 医学研究科, 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) |
2008 – 2010
|
| Keywords | 腎臓学 |
|---|
| Research Abstract |
Natriuretic peptide family (ANP, BNP, and CNP) exert potent diuretic, natriuretic and vasorelaxing properties, as well as the inhibition of the renin-angiotensin-aldosterone system. We investigated the role of natriuretic peptides in renal disease and its complications.
1. Preparation of CNP-transgenic mice (CNP-Tg) and effects of CNP on renal injury :
CNP acts as a local hormone in the vessel, bone and kidney. Human SAP promoter-driven CNP-Tg exhibited enhanced bone growth as a result of excess circulating CNP. CNP-Tg showed ameliorated renal fibrosis and macrophage infiltration upon obstructive nephropathy model.
2. Role of GC-A (a receptor for ANP and BNP) and aldosterone in glomerular injury :
GC-A is expressed abundantly 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 the MR antagonist, ARB or antioxidant.
3. Role of ANP and BNP in peritoneal sclerosis :
Peritoneal sclerosis is a serious complication in chronic peritoneal dialysis, but the effective treatment is not established yet. Subcutaneous ANP administration as well as chronic BNP excess in transgenic mice effectively ameliorated peritoneal adhesion in a mouse model of peritoneal sclerosis.
These results indicate that natriuretic peptides will have a various therapeutic potential in renal disease and related pathophysiological conditions.
|
-
[Journal Article] Circulating C-type natriuretic peptide (CNP) rescues chondrodysplastic CNP knockout mice from their impaired skeletal growth and early death.2010
Author(s)
Fujii T, Komatsu Y, Yasoda A, Kondo E, Yoshioka T, Nambu T, Kanamoto N, Miura M, Tamura N, Arai H, Mukoyama M, Nakao K
-
Journal Title
Endocrinology 151
Pages: 4381-4388
Peer Reviewed
-
[Journal Article] Podocyte-specific expression of tamoxifeninducible Cre recombinase in mice.2010
Author(s)
Yokoi H, Kasahara M, Mukoyama M, Mori K, Kuwahara K, Fujikura J, Arai Y, Saito Y, Ogawa Y, Kuwabara T, Sugawara A, Nakao K.
-
Journal Title
Nephrol Dial Transplant 25
Pages: 2120-2124
Peer Reviewed
-
-
[Journal Article] Chronically elevated plasma C-type natriuretic peptide level stimulates skeletal growth in transgenic mice.2009
Author(s)
Kake T, Kitamura H, Adachi Y, Yoshioka T, Watanabe T, Matsushita H, Fujii T, Kondo E, Tachibe T, Kawase Y, Jishage K, Yasoda A, Mukoyama M, Nakao K
-
Journal Title
Am J Physiol Endocr Metab 297
Pages: E1339-E1348
Peer Reviewed
-
-
[Journal Article] Urinary neutrophil gelatinase-associated lipocalin levels reflect damage to glomeruli, proximal tubules, and distal nephrons.2009
Author(s)
Kuwabara T, Mori K, Mukoyama M, Kasahara M, Yokoi H, Saito Y, Yoshioka T, Ogawa Y, Imamaki H, Kusakabe T, Ebihara K, Omata M, Satoh N, Sugawara A, Barasch J, Nakao K
-
Journal Title
Kidney Int 75
Pages: 285-294
Peer Reviewed
-
[Journal Article] Adrenomedullin inhibits connective tissue growth factor expression, extracellular signal- regulated kinase activation and renal fibrosis.2008
Author(s)
Nagae T, Mori K, Mukoyama M, Kasahara M, Yokoi H, Suganami T, Sawai K, Yoshioka T, Koshikawa M, Saito Y, Ogawa Y, Kuwabara T, Tanaka I, Sugawara A, Kuwahara T, Nakao K
-
Journal Title
Kidney Int 74
Pages: 70-80
Peer Reviewed
-
[Presentation] Atrial natriuretic peptide prevents peritoneal adhesion formation with inhibiting macrophage and CD3-positive cell infiltration.2010
Author(s)
Yokoi H, Kasahara M, Mori K, Kuwabara T, Imamaki H, Kawanishi T, Koga K, Ishii A, Mori K, Kato Y, Sugawara A, Mukoyama M, Nakao K
Organizer
第43回米国腎臓学会学術集会
Place of Presentation
デンバー、アメリカ
Year and Date
2010-11-18
-
-
[Presentation] Natriuretic peptide receptor guanylyl cyclase-A signaling exerts antagonistic effects on the local renin-angiotensin- aldosterone system in kidney.2010
Author(s)
Ogawa Y, Mukoyama M, Yokoi H, Kasahara M, Mori K, Yoshioka T, Saito Y, Kuwabara T, Imamaki H, Kawanishi T, Koga K, Ishii A, Kishimoto I, Sugawara A, Nakao K
Organizer
国際腎臓学会Nexus Symposium 2010
Place of Presentation
京都
Year and Date
2010-04-16
-
-
[Presentation] Protective effects of natriuretic peptide receptor guanylyl cyclase-A signaling on aldosteroneinduced glomerular injury.2009
Author(s)
Mukoyama M, Ogawa Y, Yokoi H, Kasahara M, Mori K, Yoshioka T, Saito Y, Kuwabara T, Imamaki H, Kishimoto I, Sugawara A, Nakao K
Organizer
2009年世界腎臓学会
Place of Presentation
ミラノ、イタリア
Year and Date
2009-05-25
-
[Presentation] Protective effect of atrial natriuretic peptide receptor guanylyl cyclase-A signaling on aldosteroneinduced renal injury.2008
Author(s)
Ogawa Y, Mukoyama M, Yokoi H, Kasahara M, Mori K, Yoshioka T, Saito Y, Kuwabara T, Imamaki H, Sugawara A, Nakao K
Organizer
第41回米国腎臓学会学術集会
Place of Presentation
フィラデルフィア、アメリカ
Year and Date
2008-11-06
-
-
