2010 Fiscal Year Final Research Report
MOLECULAR MECHANISM OF GLOMERULOSCLEROSIS IN AGING
| Project/Area Number |
21790808
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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 |
Kidney internal medicine
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
ARAI Hidenori 京都大学, 医学研究科, 教授 (60232021)
ABE Hideharu 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 准教授 (60399342)
DOI Toshio 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (60183498)
IEHARA Noriyuki 京都大学, 医学研究科, 助教 (20281727)
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| Research Collaborator |
NAGAI Kojiro 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教
MIMA Akira 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 助教
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| Project Period (FY) |
2009 – 2010
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| Keywords | 老化 / 細胞・組織 / 病理学 |
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| Research Abstract |
Glomerulosclerosis is the most common cause of chronic renal failure in aging. It is pathologically characterized by the accumulation of extracellular matrix in mesangium, of which main component is type IV collagen (Col4). Recently, we identified Smad1 as a direct regulator of Col4 under diabetic condition in vitro. To elucidate the mechanism of glomerulosclerosis in aging, we addressed the role of Smad1 in glomerulosclerosis during diabetes. First, we showed overexpression of Smad1 exacerbates glomerulosclerosis in diabetic mice, and identified bone morphogenetic protein 4 (BMP4) as a potent stimulator of Smad1 during diabetes. Now we are checking the role of BMP4 for biological aging process. Id (Inhibitor of differentiation), one of the important transcriptional factors regulated by Smad1, is known to inhibit basic-helix loop helix protein such as E2A, and to regulate cellular senescence. We showed that PIASy, which was also identified as a regulator of cellular senescence, is also a novel E2A binding partner, and enhances its sumoylation as a specific SUMO-E3 ligase, leading to down-regulate phenotypic changes of mesangial cells.
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Research Products
(18 results)
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[Journal Article] SOX9 protein induces a chondrogenic phenotype of mesangial cells and contributes to advanced diabetic nephropathy2011
Author(s)
Kishi S, Abe H, Akiyama H, Tominaga T, Murakami T, Mima A, Nagai K, Kishi F, Matsuura M, Matsubara T, Iehara N, Ueda O, Fukushima N, Jishage K, Doi T
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Journal Title
J Biol Chem.
Volume: 286(37)
Pages: 32162-9
DOI
Peer Reviewed
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[Journal Article] Activation of bone morphogenetic protein 4 signaling leads to glomerulosclerosis that mimics diabetic nephropathy2011
Author(s)
Tominaga T, Abe H, Ueda O, Goto C, Nakahara K, Murakami T, Matsubara T, Mima A, Nagai K, Araoka T, Kishi S, Fukushima N, Jishage K, Doi T
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Journal Title
J Biol Chem.
Volume: 286(22)
Pages: 20109-16
DOI
Peer Reviewed
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[Journal Article] Activation of Src mediates PDGF-induced Smad1 phosphorylation and contributes to the progression of glomerulosclerosis in glomerulonephritis2011
Author(s)
Mima A, Abe H, Nagai K, Arai H, Matsubara T, Araki M, Torikoshi K, Tominaga T, Iehara N, Fukatsu A, Kita T, Doi T
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Journal Title
PLoS One.
Volume: 6(3)
Pages: e17929
DOI
Peer Reviewed
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[Presentation] Overexpression of Smad1 Causes Remarkable Glomerulosclerosis in Diabetic Mice2010
Author(s)
Takeshi Matsubara, Hideharu Abe, Otoya Ueda, Kou-ichi Jishage, Akira Mima, Chisato Goto, Tatsuya Tominaga, Makoto Araki, Kazuo Torikoshi, Kojiro Nagai, Noriyuki Iehara, Atsushi Fukatsu, Naoshi Fukushima, Hidenori Arai, Toshio Doi
Organizer
the American Diabetes Association's 70th Scientific Sessions
Place of Presentation
Orlando, FL, USA
Year and Date
2010-06-26
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