The investigation on the involvement of TGF-beta signal transduction in fibrosis
| Project/Area Number |
16K10165
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
皮膚科学
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| Research Institution | Kumamoto University |
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Principal Investigator |
IHN HIRONOBU 熊本大学, 大学院生命科学研究部(医), 教授 (20282634)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 遺伝子 / 細胞・組織 / シグナル伝達 / 皮膚免疫・炎症学 |
|---|
| Outline of Final Research Achievements |
We identified the molecules up-regulated or down-regulated with cDNA microarray analyses using skin sections and cultured dermal fibroblasts from patients with systemic sclerosis (SSc). We also identified microRNAs up-regulated or down-regulated with microRNA array analyses in SSc. We identified the such molecules in integrinαVβ5 stable transfectants and TSP-1 stable transfectants. And we investigated the function of these microRNAs. We established TSP-1 transgenic mice using collagen promoter/ enhancer, and confirmed the extent of the over-expression of it in each organ. We investigated the skin, lung, and liver histologically, and inverstigated the expression of various molecules. And we investigated the existence of M2 macrophagesand the expression of B cell markers, Th2 cytokine, and interleukin-17
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| Academic Significance and Societal Importance of the Research Achievements |
線維化の機序は未だ明らかでなく、線維化の治療も未だ確立せず、本邦においても、世界中でも多くの方が線維化を伴う疾患に罹患し、苦しみ、また結果として死を迎えている。線維化は、TGFβおよびTGFβ情報伝達の関与が考えられているが、その詳細は明らかではない。本研究により、線維化に対するTGFβ情報伝達の関与が詳細に明らかになれば、線維化治療のターゲット明らかになり、線維化治療法の開発が進み、学術的にも社会的にも大きなインパクトがある。
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Report
(3 results)
Research Products
(195 results)
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[Journal Article] Overexpression of cyclin-dependent kinase 4 protein in extramammary Paget's disease.2019
Author(s)
Urata K, Kajihara I, Myangat TM, Tasaki Y, Otsuka-Maeda S, Sawamura S, Kanazawa-Yamada S, Sakamoto R, Makino K, Aoi J, Igata T, Makino T, Masuguchi S, Fukushima S, Jinnin M, Ihn H
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Journal Title
The Journal of dermatology
Volume: 印刷中
DOI
Related Report
Peer Reviewed
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[Journal Article] Serum concentrations of HGF are correlated with response to anti-PD-1 antibody therapy in patients with metastatic melanoma2019
Author(s)
Kubo Y, Fukushima S, Inamori Y, Tsuruta M, Egashira S, Yamada-Kanazawa S, Nakahara S, Tokuzumi A, Miyashita A, Aoi J, Kajihara I, Tomita Y, Wakamatsu K, Jinnin M, Ihn H
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Journal Title
Journal of Dermatological Science
Volume: 93
Pages: 33-10
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Recurrent Fusion Gene ADCK4-NUMBL in Cutaneous Squamous Cell Carcinoma Mediates?Cell?Proliferation2019
Author(s)
Egashira S, Jinnin M, Makino K, Ajino M, Shimozono N, Okamoto S, Tazaki Y, Hirano A, Ide M, Kajihara I, Aoi J, Harada M, Igata T, Masuguchi S, Fukushima S, Ihn H
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Journal Title
Journal of Investigative Dermatology
Volume: 139
Pages: 954-957
DOI
Related Report
Peer Reviewed
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[Journal Article] Differential Roles of Rad18 and Chk2 in Genome Maintenance and Skin Carcinogenesis Following UV Exposure.2018
Author(s)
Tanoue, Y., Toyoda, T., Sun, J, Mustofa, M.K., Tateishi, C., Endo, S., Motoyama, N., Araki, K., Wu, D., Okuno, Y., Tsukamoto, T., Takeya, M., Ihn, H., Vaziri, C., Tateishi, S.
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Journal Title
J Invest Dermatol
Volume: 138
Pages: 2550-2557
DOI
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Peer Reviewed / Int'l Joint Research
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[Journal Article] Immune checkpoint inhibitors in the onset of myasthenia gravis with hyperCKemia2018
Author(s)
Koutaro Takamatsu, Shunya Nakane, Shigeaki Suzuki, Takayuki Kosaka, Satoshi Fukushima, Toshihiro Kimura, Azusa Miyashita, Akihiro Mukaino, Shiori Yamakawa, Keisuke Watanabe, Masatoshi Jinnin, Yoshihiro Komohara, Hironobu Ihn, and Yukio Ando
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Journal Title
Annals of Clinical and Translational Neurology
Volume: 5
Pages: 1421-1427
DOI
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Peer Reviewed / Open Access
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[Journal Article] The role of miR-210, E2F3 and ephrin A3 in angiosarcoma cell proliferation.2017
Author(s)
Nakashima S, Jinnin M, Kanemaru H, Kajihara I, Igata T, Okamoto S, Tazaki Y, Harada M, Masuguchi S, Fukushima S, Masuzawa M, Amoh Y, Masuzawa M, Ihn H.
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Journal Title
Eur J Dermatol.
Volume: 27
Pages: 464-471
DOI
Related Report
Peer Reviewed
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[Journal Article] Transethnic meta-analysis identifies GSDMA and PRDM1 as susceptibility genes to systemic sclerosis2017
Author(s)
Terao C, Kawaguchi T, Dieude P, Varga J, Kuwana M, Hudson M, Kawaguchi Y, Matucci-Cerinic M, Ohmura K, Riemekasten G, Kawasaki A, Airo P, Horita T, Oka A, Hachulla E, Yoshifuji H, Caramaschi P, Hunzelmann N, Baron M, Atsumi T, Hassoun P, Torii T, Takahashi M, et al.
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Journal Title
Ann Rheum Dis
Volume: 印刷中
Pages: 1150-1158
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Achieved good response of S-1 and docetaxel combination chemotherapy in two patients with metastatic extramammary Paget's disease2017
Author(s)
Egashira S, Kajihara I, Kanemaru H, Uemura-Kiyohara M, Yamada-Kanazawa S, Nakahara S, Nagamoto E, Fukushima S, Jinnin M, Inoue Y, Ihn H.
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Journal Title
The Journal of Dermatology
Volume: 44
DOI
Related Report
Peer Reviewed
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[Journal Article] A randomized double-blind trial of intravenous immunoglobulin for bullous pemphigoid2017
Author(s)
Amagai M, Ikeda S, Hashimoto T, Mizuashi M, Fujisawa A, Ihn H, Matsuzaki Y, Ohtsuka M, Fujiwara H, Furuta J, Tago O, Yamagami J, Tanikawa A, Uhara H, Morita A, Nakanishi G, Tani M, Aoyama Y, Makino E, Muto M, Manabe M, et al.
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Journal Title
J Dermatol Sci.
Volume: 85（2）
Pages: 77-84
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Dysregulated interleukin-23 signalling contributes to the increased collagen production in scleroderma fibroblasts via balancing microRNA expression2017
Author(s)
Nakayama W, Jinnin M, Tomizawa Y, Nakamura K, Kudo H, Inoue K, Makino K, Honda N, Kajihara I, Fukushima S, Ihn H.
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Journal Title
Rheumatology
Volume: 56
Pages: 145-155
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Diagnosis of nail psoriasis: evaluation of nail-derived microRNAs as potential novel biomarker2017
Author(s)
Wang Z, Jinnin M, Harada M, Kudo H, Inoue K, Nakayama W, Honda N1, Makino K1, Kajihara I, Fukushima S, Ihn H
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Journal Title
Eur J Dermatol.
Volume: 1
Pages: 20-27
DOI
Related Report
Peer Reviewed
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[Journal Article] Anorectal malignant melanoma with extensive intraepithelial extension: report of a case.2017
Author(s)
Umezaki N, Ishimoto T, Koba I, Nakaya T, Mawatari M, Kuramoto K, Izumi D, Sakamoto Y, Miyamoto Y, Yoshida N, Watanabe M, Inoue Y, Ihn H, Baba H.
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Journal Title
Int Canc Conf J
Volume: 印刷中
Related Report
Peer Reviewed
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[Presentation] Serum levels of soluble programmed death-ligand 1 in patients with metastatic melanoma treated with anti-programmed death-ligand 1 antibodies.2018
Author(s)
Fukushima S, Inamori Y, Kubo Y, Nakahara S, Miyashita A, Kadoshita M, Tokuzumi A, Masuguchi S, Niimori D, Jinnin M, Ihn H.
Organizer
The 13 th Meeting og German-Japanese Society of Dermatology
Related Report
Int'l Joint Research
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[Presentation] Topline results from phase II of combination treatment with canerpaturev (HF10), an oncolytic viral immunotherapy, and ipilimumab in patients with unresectable or metastatic melanoma after anti-PD-1 therapy.2018
Author(s)
Isei T, Yokota K, Uhara H, Fujisawa Y, Takenouchi T, Kiyohara Y, Uchi H, Saruta H, Ihn H, Inozume T, Watanabe D, Takahashi A, Fukushima S, Tanaka M, Y amazaki N.
Organizer
ESMO 2018
Related Report
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[Presentation] A novel small compound HPH-15 antagonizes TGF-β/Smad signaling and ameliorates experimental skin fibrosis.2017
Author(s)
Luong VH, Chino T, Tokuriki A, Oyama N, Sasaki Y, Ogura D, Niwa S, Fujita M, Okamoto M, Otsuka M, Ihn H, Hasegawa M.
Organizer
76 th Annual Meeting of Society for Investigative Dermatology
Related Report
Int'l Joint Research
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[Presentation] Intratumoral expression levels of PD-L1, GZMA, and HLA-A along with oligoclonal T cell expansion associate with response to nivolmab against melanomas.2017
Author(s)
Fukushima S, Inoue H, Park JH, Kiyotani K, Zewde M, Miyashita A, Jinnin M, Kiniwa Y, Okuyama R, Tanaka R, Fujisawa Y, Kato H, Morita A, Asai J, Katoh N, Yokota K, Akiyama M, Ihn H, Nakamura Y.
Organizer
第21回日本がん免疫学会総会
Related Report
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[Presentation] Immune biomarkers to predict response of nivolimab, intratumoral gene expression and T cell receptor repertoire analysis.2017
Author(s)
Fukushima S, Inoue H, Park J, Kiyotani K, Kiniwa Y, Fujisawa Y, Kato H, Asai J, Yokota K, Ihn H, Nakamura Y.
Organizer
47 th Annual ESDR Meeting 2017
Related Report
Invited
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[Presentation] A novel TGF-β/Smad signaling inhibitor ameliorates bleomycin-induced skin fibrosis.2017
Author(s)
Hasegawa M, Luong VH, Chino T, Oyama N, Sasaki Y, Ogura D, Niwa S, Fujita M, Okamoto Y, Otsuka M, Ihn H.
Organizer
47 th Annual ESDR Meeting 2017
Related Report
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[Presentation] RXRB is a MHC-encoded susceptibility gene associated with anti-topoisomerase I antibody-positive systemic sclerosis.2017
Author(s)
Oka A, Asano Y, Hasegawa M, Fujimoto M, Ishikawa O, Kuwana M, Kawaguchi Y, Yamamoto T, Takahashi H, Goto D, Endo H, Jinnin M, Takehara K, Sato S, Ihn H.
Organizer
42 th Annual Meeting of the Japanese Society for Investigative Dermatology
Related Report
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[Book] 炎症と免疫2017
Author(s)
尹浩信
Total Pages
97
Publisher
先端医学社
ISBN
4865502734
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