2014 Fiscal Year Annual Research Report
線維化におけるTGF-β情報伝達の関与についての分子基盤の解明
Project/Area Number |
24591658
|
Research Institution | Kumamoto University |
Principal Investigator |
尹 浩信 熊本大学, 生命科学研究部, 教授 (20282634)
|
Project Period (FY) |
2012-04-01 – 2015-03-31
|
Keywords | 遺伝子 / 細胞・組織 / シグナル伝達 |
Outline of Annual Research Achievements |
全身性強皮症、肺線維症の組織および病変部の培養線維芽細胞においてDNA microarry法にて過剰発現する分子、発現低下する分子を検討し、またrealtime PCRを用いたmicro RNA arrayによって過剰発現するmicro RNA、発現低下するmicro RNAを同定した。 正常皮膚線維芽細胞を用いてintegrinαVβ5 stable transfectant作成し、integrin αVβ5の過剰発現を確認した。 COL1A2 enhancer、promoterをベクターに組み込んで作成したtransgeneを用いて線維芽細胞特異的integrin αVβ5 transgenic mouseを作成し、phenotypeを解析したが、予想に反して皮膚の線維化は認められず、正常マウスと比較して皮膚厚の減少を認めた。 integrin αVβ5 stable transfectantを用いてDNA microarry法、realtime PCRを用いたmicro RNA array法、情報伝達protein arrayを行い、線維化phenotypeを形成しているか、すなわちTGF-β受容体が過剰発現しているか、TGF-β情報伝達経路(Smad2、Smad 3、Smad4、p300/CBP、p38 MAPK、PI3 kinase)が過剰リン酸化しているか、I型コラーゲンをはじめとする細胞外マトリックス蛋白および遺伝子が過剰発現しているか、MMP-1などのproteaseの発現が低下しているか、TIMP-1などのprotease inhibitorの発現が亢進しているか詳細に検討し、autocrine TGF-β signalingによりI型コラーゲンをはじめとする細胞外マトリックス蛋白および遺伝子が過剰発現し、MMP-1などのproteaseの発現が低下していることを確認した。
|
-
-
-
-
-
-
-
-
-
-
-
[Journal Article] Serum adhesion molecule levels as prognostic markers in patients with early systemic sclerosis: a multicenter, prospective, observational study.2014
Author(s)
Hasegawa M, Asano Y, Endo H, Fujimoto M, Goto D, Ihn H, Inoue K, Ishikawa O, Kawaguchi Y, Kuwana M, Ogawa F, Takahashi H, Tanaka S, Sato S, Takehara K.
-
Journal Title
PLoS One
Volume: 9
Pages: e88150-e88150
Peer Reviewed
-
[Journal Article] Angiopoietin-like protein 2 accelerates carcinogenesis by activating chronic inflammation and oxidative stress.2014
Author(s)
Aoi J, Endo M, Kadomatsu T, Miyata K, Ogata A, Horiguchi H, Odagiri H, Matsuda T, Fukushima S, Jinnin M, Hirakawa S, Sawa T, Akaike T, Ihn H, Oike Y.
-
Journal Title
Mol Cancer Res
Volume: 12
Pages: 239-247
Peer Reviewed
-
-
-
[Journal Article] Up-regulation of miR-18a contributes to the epidermal necrolysis in severe drug eruptions.2014
Author(s)
Ichihara A, Wang Z, Jinnin M, Izono Y, Shimozono N, Yamane K, Fujisawa A, Moriya C, Fukushima S, Inoue Y, Ihn H.
-
Journal Title
J Allergy Clin Immunol
Volume: 133
Pages: 1065-1074
Peer Reviewed
-
-
-
-
[Journal Article] Knockout of endothelial cell-derived endothelin-1 attenuates skin fibrosis but accelerate cutaneous wound healing.2014
Author(s)
Makino K, Jinnin M, Aoi J, Kajihara I, Makino T, Fukushima S, Sakai K, Nakayama K, Emoto N, Yanagisawa M, Ihn H.
-
Journal Title
PLoS One
Volume: 9
Pages: e97972-e97972
Peer Reviewed
-
[Journal Article] Decreased IL-20 expression in scleroderma skin contributes to cutaneous fibrosis.2014
Author(s)
Kudo H, Jinnin M, Asano Y, Trojanowska M, Nakayama W, Inoue K, Honda N, Kajihara I, Makino K, Fukushima S, Ihn H.
-
Journal Title
Arthritis Rheumatol
Volume: 65
Pages: 1636-1647
Peer Reviewed
-
[Journal Article] Evaluation of sentinel node biopsy for cutaneous squamous cell carcinoma.2014
Author(s)
Fukushima S, Masuguchi S, Igata T, Harada M, Aoi J, Miyashita A, Nakahara S, Inoue Y, Jinnin M, Shiraishi S, Yamashita Y, Ishihara T, Ihn H.
-
Journal Title
J Dermatol
Volume: 41
Pages: 539-541
Peer Reviewed
-
-
-
-
-
[Journal Article] The proportion of lymphocytic inflammation with CD123-positive cells in lupus erythematosus profundus predict a clinical response to treatment.2014
Author(s)
Miyashita A, Fukushima S, Makino T, Yoshino Y, Yamashita J, Honda N, Aoi J, ,Ichihara A, Jinnin M, Inoue Y, Ihn H.
-
Journal Title
Acta Derm Venereol
Volume: 94
Pages: 563-567
Peer Reviewed
-
-
[Journal Article] Down-regulation of microRNA-196a in the sera and involved skin of localized scleroderma patients.2014
Author(s)
Makino T, Jinnin M, Etoh M, Yamane K, Kajihara I, Makino K, Ichihara A, Igata T, Sakai K, Fukushima S, Ihn H.
-
Journal Title
Eur J Dermatol
Volume: 24
Pages: 470-476
Peer Reviewed
-
-
-
-
-
[Journal Article] Increased CCL22 expression in psoriatic skin predicts a good response to infliximab therapy.2014
Author(s)
Kusumoto S, Kajihara I, Nagatomo E, Makino K, Ichihara A, Aoi J, Johno T, Makino T, Fukushima S, Jinnin M, Ihn H.
-
Journal Title
Br J Dermatol
Volume: 171
Pages: 1259-1261
Peer Reviewed
-
[Journal Article] The expression profile of the toll-like receptor family in scleroderma dermal fibroblasts.2014
Author(s)
Sakoguchi A, Nakayama W, Jinnin M, Wang Z, Yamane K, Aoi J, Makino K, Kajihara I, Ichihara A, Makino T, Fukushima S, Sakai K, Inoue Y, Ihn H.
-
Journal Title
Clin Exp Rheumatol
Volume: 32
Pages: S4-S9
-
-
-
-
-
-
-
[Presentation] Down-regulation of microRNA-196a in the sera and involved skin of localized scleroderma patients.2014
Author(s)
Makino T, Jinnin M, Etoh M, Yamane K, Kajihara I, Makino K, Ichihara A, Igata T, Sakai K, Fukushima S, Ihn H.
Organizer
ACR
Place of Presentation
Boston
Year and Date
2014-11-14 – 2014-11-19
-
[Presentation] Potential use of polysaccharide as a skin care material for atopic dermatitis.2014
Author(s)
Tanaka T, Tanida Y, Hayashi T, Motoyama K, Higashi T, Kaneko S, Ishitsuka Y, Irie T, Kaneko T, Okajima M, Ihn H, Arima H.
Organizer
International Federation of Societies of Cosmetic Chemists in Paris
Place of Presentation
Paris
Year and Date
2014-10-27 – 2014-10-30
-
-
-
-
-
-
-
-