2013 Fiscal Year Final Research Report
The role of C1q and Wnt signaling in aging and diabetes
| Project/Area Number |
23689038
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
General internal medicine (including Psychosomatic medicine)
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| Research Institution | The University of Tokyo (2013)
Osaka University (2011-2012) |
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Principal Investigator |
NAITO Atsuhiko 東京大学, 医学部附属病院, 助教 (10588891)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Keywords | 老化 / Wntシグナル / 心不全 / 糖尿病 / C1q |
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| Research Abstract |
Aging is associated with various diseases, including diabetes mellitus and heart failure. However, the molecular mechanism of aging is not known yet. In the present study, we identified that complement C1q, which plays an important role in immune system, increases with advancing age and plays a pivotal role in aging and in the pathophysiology of various 'aging-associated disorders'. Complement C1q impairs skeletal muscle regeneration through activation of Wnt signaling and inhibition of C1q-induced Wnt signaling activation recovered the regenerative capacity of the aged mice. Elevation of C1q is also observed in obesity- and aging-induced diabetes, and may play causative role in pathogenesis of diabetes. We also identified that C1q expression is increased during heart failure and that cardiomyocyte-specific and endothelial cell-specific Wnt signaling activation leads to progressive cardiac dysfunction and heart failure.
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[Journal Article] Notch activation mediates angiotensin II-induced vascular remodeling by promoting the proliferation and migration of vascular smooth muscle cells2013
Author(s)
Ozasa Y, Akazawa H, Qin Y, Tateno K, Ito K, Kudo-Sakamoto Y, Yano M, Yabumoto C, Naito AT, Oka T, Lee JK, Minamino T, Nagai T, Kobayashi Y, Komuro I
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Journal Title
Hypertens Res
Volume: (10)
Pages: 859-65
DOI
Peer Reviewed
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[Journal Article] Complement C1q activates canonical Wnt signaling and promotes aging-related phenotypes2012
Author(s)
Naito AT, Sumida T, Nomura S, Liu ML, Higo T, Nakagawa A, Okada K, Sakai T, Hashimoto A, Hara Y, Shimizu I, Zhu W, Toko H, Katada A, Akazawa H, Oka T, Lee JK, Minamino T, Nagai T, Walsh K, Kikuchi A, Matsumoto M, Botto M, Shiojima I, Komuro I
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Journal Title
Cell
Volume: 149(6)
Pages: 1298-313
DOI
Peer Reviewed
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[Journal Article] Agonist-independent constitutive activity of angiotensin II receptor promotes cardiac remodeling in mice2012
Author(s)
Yasuda N, Akazawa H, Ito K, Shimizu I, Kudo-Sakamoto Y, Yabumoto C, Yano M, Yamamoto R, Ozasa Y, Minamino T, Naito AT, Oka T, Shiojima I, Tamura K, Umemura S, Paradis P, Nemer M, Komuro
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Journal Title
Hypertension
Volume: 59(3)(Epub 2012 Jan 30)
Pages: 627-33
DOI
Peer Reviewed
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