Clarifiation of CKD progression by regulating fibrotic microenvironment
Project/Area Number |
20K08605
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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 |
Review Section |
Basic Section 53040:Nephrology-related
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Research Institution | Kanazawa University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
和田 隆志 金沢大学, その他部局等, その他 (40334784)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | 線維化 / 線維芽細胞 / 接着斑 / 腎不全 / 慢性腎臓病 |
Outline of Research at the Start |
臓器不全の共通進展機序である線維化の病理学的共通所見として、線維芽細胞集積と細胞外基質沈着がある。本研究は、線維化組織微小環境に着目して、線維化進展機序の解明および診断・治療法開発を目指す。申請者はこれまで、アクチン細胞骨格の生物学的役割に着目し、アクチン細胞骨格依存性の細胞内シグナル伝達機構が臓器線維化にはたす意義を報告してきた。近年、アクチン細胞骨格は、細胞と細胞外基質との接着装置である接着斑に結合することで、微小環境の形成に関与することが明らかとなっている。以上より、線維化組織微小環境に焦点をあて、アクチン細胞骨格依存性細胞内シグナル伝達の線維化にはたす意義を解明する。
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Outline of Final Research Achievements |
Fibrosis is characterized by an excessive wound healing response to organ damage, causing extracellular matrix deposition and accumulation of fibroblasts/myofibroblasts. In the process of enal failure, various renal diseases are characterized by taking a common process which is renal fibrosis. In this study, we attempted to elucidate the significance of cytoskeleton-dependent signal for renal fibrosis by regulating the biological properties of renal fibroblasts. As a result, it was revealed that the cytoskeleton-dependent MRTF-SRF signal by TGF-b1 in renal fibroblasts contributes to the expression of focal adhesion components and extracellular matrix such as colalgen and fibronectin. In addition, systemic MRTF-A- and fbroblast-specific MRTF-B- deficiency attenuates renal fibrosis by inhibiting the expression of focal adhesion components and extracellular matrix. Tese results suggest that MRTF-SRF signaling in fibroblast might be a target to combat renal fibrosis.
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Academic Significance and Societal Importance of the Research Achievements |
本研究では、細胞骨格に関連するMRTF-SRFシグナルが、腎臓を構成する線維芽細胞機能を調節することで腎不全の原因となる線維化に関与するかを試みた。その結果、腎線維芽細胞において、MRTF-SRFシグナルが、腎線維芽細胞を活性化させ、腎線維化進展に寄与することを明らかにした。これは腎障害の原因に関わらない共通進展機序であり、現在増加の一途を辿っている末期腎不全患者数の抑制につながる新規治療法開発につながることが期待される。
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] Intra-brain and plasma levels of L-Serine are associated with cognitive status in patients with CKD. Kid Dis2023
Author(s)
〇Iwata Y*, Nakade Y, Kinoshita M, Sabit H, Nakajima R, Furuichi K, Mita M, Nakane M, Sakai N, Kitajima S, Toyama T, Miyagawa T, Hara A, Shimizu M, Sato K, Oshima M, Nakagawa S, Yamamura Y, Ogura H, Koshino Y, Nakada M, Wada T.
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Journal Title
Kidney Dis (Basel) .
Volume: 9
Issue: 2
Pages: 118-129
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Increased levels of oral Streptococcus-derived D-alanine in patients with chronic kidney disease and diabetes mellitus.2022
Author(s)
Nakade Y, Iwata Y*, Sakai N, Mita M, Nakane M, Hamase K, Suda W, Toyama T, Kitajima S, Hara A, Shimizu M, Ogushi C, Furuichi K, Koshino Y, Morita H, Hattori M, Wada T.
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Journal Title
Sci Rep
Volume: 12
Issue: 1
Pages: 21773-21773
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Deep learning analysis of clinical course of primary nephrotic syndrome: Japan Nephrotic syndrome cohort study (JNSCS).2022
Author(s)
Kimura T, Yamamoto R, Yoshino M, Sakate R, Imai E, Maruyama S, Yokoyama H, Sugiyama H, Nitta K, Tsukamoto T, Uchida S, Takeda A, Sato T, Wada T, Hayashi H, Akai Y, Fukunaga M, Tsuruya K, Masutani K et al.
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Journal Title
Clinical and Experimental Nephrology
Volume: 26
Issue: 4
Pages: 1170-1179
DOI
Related Report
Peer Reviewed
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[Journal Article] Cyclin-dependent kinase 4-related tubular epithelial cell proliferation is regulated by Paired box gene 2 in renal ischemia-reperfusion injury2022
Author(s)
Sako K, Furuichi K, Makiishi S, Yamamura Y, Okumura T, Le T, Kitajima S, Toyama T, Hara A, Iwata Y, Sakai N, Shimizu M, Niimura F, Matsusaka T, Kaneko S, Wada T.
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Journal Title
Kidney International
Volume: -
Issue: 1
Pages: 45-57
DOI
Related Report
Peer Reviewed
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[Journal Article] D-Serine inhibits the attachment and biofilm formation of methicillin-resistant Staphylococcus aureus2021
Author(s)
Iwata Y, Sakai N, Yoneda I, Senda Y, Sakai-Takemori Y, Oshima M, Nakagawa-Yoneda S, Ogura H, Sato K, Minami T, Kitajima S, Toyama T, Yamamura Y, Miyagawa T, Hara A, Shimizu M, Furuichi K, Matsushima K, Wada T.
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Journal Title
Biochem Biophys Res Commun.
Volume: 22
Pages: 50-56
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Identification of candidate PAX2-regulated genes implicated in human kidney development2021
Author(s)
Yuta Yamamura, Kengo Furuichi, Yasuhiro Murakawa, Shigeki Hirabayashi, Masahito Yoshihara, Keisuke Sako, Shinji Kitajima, Tadashi Toyama, Yasunori Iwata, Norihiko Sakai, Kazuyoshi Hosomichi, Philip M Murphy, Atsushi Tajima, Keisuke Okita, Kenji Osafune, Shuichi Kaneko, Takashi Wada
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Journal Title
Scientific reports
Volume: 11
Issue: 1
Pages: 9123-9123
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Higher serum levels of autotaxin and phosphatidylserine-specific phospholipase A 1 in patients with lupus nephritis2021
Author(s)
Iwata Y, Kitajima S, Yamahana J, Shimomura S, Yoneda-Nakagawa S, Sakai N, Furuichi K, Ogura H, Sato K, Toyama T, Yamamura Y, Miyagawa T, Hara A, Shimizu M, Ohkawa R, Kurano M, Yatomi Y, Wada T.
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Journal Title
Int J Rheum Dis.
Volume: 24
Issue: 2
Pages: 231-239
DOI
Related Report
Peer Reviewed / Open Access
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