The analysis of the skeletal cell differentiation regulated by endoplasmic reticulum stress transducers.
Project/Area Number |
24659678
|
Research Category |
Grant-in-Aid for Challenging Exploratory Research
|
Allocation Type | Multi-year Fund |
Research Field |
Orthopaedic surgery
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Research Institution | Hiroshima University |
Principal Investigator |
SAITO ATSUSHI 広島大学, 医歯薬保健学研究院, 助教 (30580394)
|
Project Period (FY) |
2012-04-01 – 2015-03-31
|
Project Status |
Completed (Fiscal Year 2014)
|
Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
|
Keywords | BBF2H7 / 小胞体ストレス応答 / Sox9 / 軟骨細胞 / 軟骨細胞分化 / ヘッジホッグシグナル / 小胞体ストレストランスデューサー / OASIS / 骨芽細胞 / 小胞体ストレス |
Outline of Final Research Achievements |
Endoplasmic reticulum (ER) stress transducer, BBF2H7, is cleaved in response to ER stress and the N-terminus acts as a transcription factor during chondrogenesis. The activated BBF2H7 promotes cartilage matrix protein secretion through the up-regulation of Sec23a, which is a target of BBF2H7. We elucidated the mechanisms of transcriptional activation of BBF2H7 in chondrocytes. Transcription of BBF2H7 is directly regulated by Sox9, a critical factor for chondrocyte differentiation that facilitates the expression of Type II collagen (Col2). Our findings demonstrate novel mechanisms of Sox9 for controlling the secretion of cartilage matrix proteins via activation of BBF2H7-Sec23a. Furthor, we demonstrated that the cleaved C-terminus is secreted to extracellular space and promotes chondrocyte proliferation via the activation of hedgehog signaling. In addition, we found that BBF2H7 activates ATF5-MCL1 pathway to avoid apoptosis during chondrogenesis.
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Report
(4 results)
Research Products
(33 results)
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[Journal Article] Promotion of cancer cell proliferation by cleaved and secreted luminal domains of ER stress transducer BBF2H7.2015
Author(s)
Iwamoto H, Matsuhisa K, Saito A, Kanemoto S, Asada R, Hino K, Takai T, Cui M, Cui X, Kaneko M, Arihiro K, Sugiyama K, Kurisu K, Matsubara A, Imaizumi K.
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Journal Title
Plos One
Volume: 10
Issue: 5
Pages: 1-17
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Master Regulator for Chondrogenesis, Sox9, Regulates Transcriptional Activation of the ER Stress Transducer BBF2H7/CREB3L2 in Chondrocytes.2014
Author(s)
Hino K, Saito A, Kido M, Kanemoto S, Asada R, Takai T, Cui M, Cui X, Imaizumi K.
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Journal Title
Journal of Biological Chemistry
Volume: 289
Issue: 20
Pages: 13810-13820
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Transcriptional Regulation of VEGFA by the Endoplasmic Reticulum Stress Transducer OASIS in ARPE-19 Cells.2013
Author(s)
Miyagi H, Kanemoto S, Saito A, Asada R, Iwamoto H, Izumi S, Kido M, Gomi F, Nishida K, Kiuchi Y, Imaizumi K.
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Journal Title
PLOS ONE
Volume: 8
Issue: 1
Pages: 55155-55155
DOI
Related Report
Peer Reviewed
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[Journal Article] Activation of OASIS family, ER stress transducers, is dependent on its stabilization2012
Author(s)
Kondo S, Hino SI, Saito A, Kanemoto S, Kawasaki N, Asada R, Izumi S, Iwamoto H, Oki M, Miyagi H, Kaneko M, Nomura Y, Urano F and Imaizumi K
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Journal Title
Cell Death Differ
Volume: 19
Issue: 12
Pages: 1939-1949
DOI
Related Report
Peer Reviewed
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