JP5830465B2 - 表皮分化マイクロrnaシグネチャーとその使用 - Google Patents
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Description
表皮分化の段階の形態的分析と生化学的マーカー(免疫組織化学)。この技術は、非常に一般的に(局所組織学)、又はマーカーによるマーカー(免疫組織化学)によって、分化における既知のタンパク質主働筋を、分析するためだけに使用され得る。肌の状態のシグネチャーを産生し得る。それは扱いにくく、調査におけるマーカーに特異的な抗体のような利用可能な特定のツールを有する必要とするが、必ずしもそうではない。更に、即時定量的な技術ではない;
トランスクリプトーム解析:この方法は健常又は疾患粗スキーの分子シグネチャーを得るために広く使用される。この技術は、サンプルのmRNA転写物の発現解析に基づく。それは、12000遺伝子までを含み得るDNAチップを使用し、非常に一般的であり得る。しかし、それは、特に高価な装置(アフィメトリクス(商標)システム)を必要とし、幾つかの欠点があるが、何よりもしばしば扱いが困難で、高性能のバイオインフォマティクスサービスによって処理しなければならない非常に膨大な量のデータを生じる;
プロテオーム解析:これは、組織に存在する全てのタンパク質の一般的な位置の広範囲の画像を提供する。それは複数の二次元電気泳動ゲル技術を使用し、したがって、非常に実行しづらい。更に、タンパク質の正確な同定は、補足の工程を必要とし、特殊技術と操作の専門性を要する非常に高価な装置を必要とする。
分化のマーカーとしてmiRNAを使用すること。メッセンジャーRNAと比較してそれらは非常に少数であることは、miRNAプロファイルが、慣例的な一般的なトランスクリプトーム方法よりもより単純、迅速及び安価に、位置について、又は組織について得ることができる;
表皮分化の障害に関連する良性又は深刻な疾患の治療の目的でモジュレータを同定するための表皮分化のmiRNA分子シグネチャーの使用。「モジュレータ」なる用語は、化学物質又は天然抽出物、複合体製剤、siRNA、antagomirのようなmiRNA阻害剤由来の物質だけでなく、光、皮膚における機械的効果、又は注射を用いた計測システムを意味する;
表皮分化又は増殖の疾患の美容又は治療的処置の目的でmiRNA又は前記miRNAのモジュレータの使用;
表皮分化の美容又は治療的処置の効果を評価するための前記miRNAシグネチャーの使用;
正常又は病的上皮の診断を実施するための表皮分化のmiRNA分子シグネチャーの使用
を提案する。
マイクロRNA(又はマイクロRnA又はmiRNA):マイクロRNAは、約20から25ヌクレオチド長、より一般的には21から24ヌクレオチドの一本差RNAである。miRNAは遺伝子からmRNA転写後に作用するリプレッサーであり:実際、メッセンジャーRNAと対になって、タンパク質への翻訳を阻害又は抑制する。
標的miRNAは次いでRISC複合体に搭載され、分解される。
hsa−miR−141:成熟miRNA:UAACACUGUCUGGUAAAGAUGG(配列番号N°1)
hsa−miR−148a:成熟miRNA:UCAGUGCACUACAGAACUUUGU(配列番号N°2)
hsa−miR−182:成熟miRNA:UUUGGCAAUGGUAGAACUCACACU(配列番号N°3)
hsa−miR−224:成熟miRNA:CAAGUCACUAGUGGUUCCGUU(配列番号N°4)
hsa−miR−26a(hsa−miR−26a−1及びhsa−miR−26a−2):成熟miRNA:UUCAAGUAAUCCAGGAUAGGCU(配列番号N°5)
hsa−miR−26b:成熟miRNA:UUCAAGUAAUUCAGGAUAGGU(配列番号N°6)
hsa−miR−361−5p:成熟miRNA:UUAUCAGAAUCUCCAGGGGUAC(配列番号N°7)
hsa−miR−425:成熟miRNA:AAUGACACGAUCACUCCCGUUGA(配列番号N°8)
hsa−miR−455−3p:成熟miRNA:GCAGUCCAUGGGCAUAUACAC(配列番号N°9)
hsa−miR−92b:成熟miRNA:UAUUGCACUCGUCCCGGCCUCC(配列番号N°10)
hsa−let−7i:成熟miRNA:UGAGGUAGUAGUUUGUGCUGUU(配列番号N°11)
hsa−miR−22:成熟miRNA:AAGCUGCCAGUUGAAGAACUGU(配列番号N°12)
hsa−miR−221:成熟miRNA:AGCUACAUUGUCUGCUGGGUUUC(配列番号N°13)
hsa−miR−222:成熟miRNA:AGCUACAUCUGGCUACUGGGU(配列番号N°14)
hsa−miR−29a:成熟miRNA:UAGCACCAUCUGAAAUCGGUUA(配列番号N°15)
hsa−miR−29b:成熟miRNA:UAGCACCAUUUGAAAUCAGUGUU(配列番号N°16)
hsa−miR−663:成熟miRNA:AGGCGGGGCGCCGCGGGACCGC(配列番号N°17)
hsa−miR−30a:成熟miRNA:UGUAAACAUCCUCGACUGGAAG(配列番号N°18)
hsa−miR−30c:成熟miRNA:UGUAAACAUCCUACACUCUCAGC(配列番号N°19)
少なくとも1個、好ましくは少なくとも2、3、5又は全てのmiRNA hsa−miR−455−3p、hsa−miR−141、hsa−miR−148a、hsa−miR−182、hsa−miR−224、hsa−miR−26a、hsa−miR−26b、hsa−miR−361−5p、hsa−miR−425及びhsa−miR−92b、又はそれらの発現の増加を引き起こすこれらのmiRNAのモジュレータ;及び/又は場合によって、
miRNA hsa−let−7i、hsa−miR−22、hsa−miR−221、hsa−miR−222、hsa−miR−29a、hsa−miR−29b、hsa−miR−663、hsa−miR−30a及びhsa−miR−30cの1つを標的化する、例えば、antagomirのようなmiRNAの阻害剤、又はそれらの発現の抑制を引き起こすこれらのmiRNAのモジュレータを含む。
少なくとも1個、好ましくは少なくとも2、3、5又は全てのmiRNA hsa−let−7i、hsa−miR−22、hsa−miR−221、hsa−miR−222、hsa−miR−29a、hsa−miR−29b、hsa−miR−663、hsa−miR−30a及びhsa−miR−30c、又はそれらの発現の増加を引き起こすこれらのmiRNAのモジュレータ;及び/又は場合によって、
miRNA hsa−miR−455−3p、hsa−miR−141、hsa−miR−148a、hsa−miR−182、hsa−miR−224、hsa−miR−26a、hsa−miR−26b、hsa−miR−361−5p、hsa−miR−425及びhsa−miR−92bの1つを標的化する、例えば、antagomirのようなmiRNAの阻害剤、又はそれらの発現の抑制を引き起こすこれらのmiRNAのモジュレータを含む。
少なくとも1個、好ましくは少なくとも2、3、5又は全てのmiRNA hsa−miR−455−3p、hsa−miR−141、hsa−miR−148a、hsa−miR−182、hsa−miR−224、hsa−miR−26a、hsa−miR−26b、hsa−miR−361−5p、hsa−miR−425及びhsa−miR−92b、又はそれらの発現の増加を引き起こすこれらのmiRNAのモジュレータ;及び/又は場合によって、
miRNA sa−let−7i、hsa−miR−22、hsa−miR−221、hsa−miR−222、hsa−miR−29a、hsa−miR−29b、hsa−miR−663、hsa−miR−30a及びhsa−miR−30cの阻害剤、又はそれらの発現の抑制を引き起こすこれらのmiRNAのモジュレータを含む。本発明の文脈でより具体的に想定されるmiRNAの阻害剤は、antagomir、miRCURY LNA(商標)マイクロRNAノックダウンプローブ(Exiqon)及びQiagenのmiScript miRNA阻害剤である。
少なくとも1個、好ましくは少なくとも2、3、5又は全てのmiRNA hsa−let−7i、hsa−miR−22、hsa−miR−221、hsa−miR−222、hsa−miR−29a、hsa−miR−29b、hsa−miR−663、hsa−miR−30a及びhsa−miR−30c、又はそれらの発現の増加を引き起こすこれらのmiRNAのモジュレータ;及び/又は場合によって、
miRNA hsa−miR−455−3p、hsa−miR−141、hsa−miR−148a、hsa−miR−182、hsa−miR−224、hsa−miR−26a、hsa−miR−26b、hsa−miR−361−5p、hsa−miR−425及びhsa−miR−92bの阻害剤、又はそれらの発現の抑制を引き起こすこれらのmiRNAのモジュレータを含む。本発明の文脈でより具体的に想定されるmiRNAの阻害剤は、antagomir、miRCURY LNA(商標)マイクロRNAノックダウンプローブ(Exiqon)及びQiagenのmiScript miRNA阻害剤である。
ヒト角化細胞の単一層培養
正常ヒト表皮角化細胞は乳房形成に由来し、マイトマイシン処理したスイス3T3繊維芽細胞の栄養層で、Rheinwald及びGreenの方法を用いて慣例的に培養した。
角質層と生存等量真皮を伴う層化分化表皮を含むインビトロで再構築した皮膚は、正常ヒト角化細胞と正常ヒト皮膚繊維芽細胞と共に産生された。
細胞分解:
単一層培養における角化細胞は、TriReagentバッファーにおける培養皿において分解された。
再構築皮膚からの再構築表皮は、ピンセットを用いて同等の上皮から分離された。この表皮はTriReagent分解バッファーにおけるガラスホモジナイザーにおいて手動で砕いた。
全RNAをグアニジンイソチオシアネート溶液ついでフェノール/クロロホルム混合物を用いた抽出の慣例的な技術を用いて抽出した。
短鎖RNAを全RNA(マイクロコンフィルター、ミリポア)から抽出し、ポリA末端を有する3’末端で延長した。蛍光ラベル化オリゴヌクレオチドを、ポリA末端に付着させた。短鎖ラベル化RNAを次いでμParaflo(商標)「MiRHuman10.0」チップ(Atactic Technologies, LC Sciences)上でハイブリダイズさせた。それらは、miRBase10.0(711個の成熟miRNA)において記録されるヒトmiRNAの全ての相補的な配列を含んでいた。配列は、チップ上で5回沈着させた。蛍光を定量し、シグナルを正規化した。蛍光の量はサンプル中の各miRNAの発現レベルを反映していた。
各miRNAの発現は、スチューデントのt検定(p<0.05)を用いて、「培養角化細胞」サンプルと「再構築表皮角化細胞」の間で統計的に比較した。
ノザンブロット
この慣例的な技術は定性的及び定量的である。それは、1つの実験の間に幾つかのmiRNAを解析することができる。この方法は、5から50μgの全RNAの使用を要する。
この方法は、miRNAの前駆体を調査することができ、成熟miRNAを調査するために適用されている。それは商業的な方法であり(アプライド バイオシステムズ タックマン マイクロRNA アッセイ)幾つかの文献で記述されている[23]。
この方法は、慣例的なmRNAのマイクロアレイのもののように、サンプルのmiRNAの相補的なcDNAの蛍光ラベル、及び既知のmiRNA配列が置かれているスライド上のこれらのラベル化したcDNAのハイブリダイゼーションに基づく[25]。
この技術は、慣例的な結合方法を使用することで、短鎖RNAが長鎖RNAより拡散し、ハイブリダイゼーションと洗浄過程において紛失するため、慣例的なmRNAのインサイツハイブリダイゼーションよりも困難である。この問題を克服するために技術は開発されており;更に、miRNAプローブは、商業的に利用可能である(Exiqon、デンマーク)[27]。
この技術では、GFP又はLacZレポーター遺伝子は、miRNAの相補的な3’UTR部分を含むプロモーターのコントロール下に置かれた。
1. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116: 281-97.
3. Alvarez-Garcia I, Miska EA. MicroRNA functions in animal development and human disease. Development 2005; 132: 4653-62.
4. O'Donnell KA, Wentzel EA, Zeller KI等. c-Myc-regulated microRNAs modulate E2F1 expression. Nature 2005; 435: 839-43.
5. Fazi F, Rosa A, Fatica A等. A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis. Cell 2005; 123: 819-31.
8. Yi R, O'Carroll D, Pasolli HA等. Morphogenesis in skin is governed by discrete sets of differentially expressed microRNAs. Nat Genet. 2006; 38: 356-62.
10. Wenguang Z, Jianghong W, Jinquan L等. A subset of skin-expressed microRNAs with possible roles in goat and sheep hair growth based on expression profiling of mammalian microRNAs. OMICS. 2007; 11: 385-96.
11. Yi R, Poy MN, Stoffel M等. A skin microRNA promotes differentiation by repressing 'stemness'. Nature 2008; 452: 225-9.
12. Sonkoly E, Wei T, Janson PC等. MicroRNAs: Novel Regulators Involved in the Pathogenesis of Psoriasis? PLoS.ONE. 2007; 2: e610.
13. Felicetti F, Errico MC, Bottero L等. The promyelocytic leukemia zinc finger-microRNA-221/-222 pathway controls melanoma progression through multiple oncogenic mechanisms. Cancer Res 2008; 68: 2745-54.
14. Ishida-Yamamoto A, Tanaka H, Nakane H等. Inherited disorders of epidermal 角質化. J Dermatol Sci 1998; 18: 139-54.
15. Hoffjan S, Stemmler S. On the role of the epidermal differentiation complex in ichthyosis vulgaris, atopic dermatitis and psoriasis. Br J Dermatol 2007; 157: 441-9.
17. Ghadially R, Brown BE, Sequeira-Martin SM等. The aged epidermal permeability barrier. Structural, functional, and lipid biochemical abnormalities in humans and a senescent murine model. J.Clin.Invest 1995; 95: 2281-90.
18. Harding CR. The stratum corneum: structure and function in health and disease. Dermatol Ther 2004; 17 Suppl 1: 6-15.
19. Marionnet C, Bernerd F, Dumas A等. Modulation of gene expression induced in human epidermis by environmental stress in vivo. J Invest Dermatol 2003; 121: 1447-58.
23. Chen C, Ridzon DA等. Real-time quantification of microRNAs by stem-loop RT-PCR. Nucleic Acids Res 2005; 33: e179.
25. Vagin VV等. A distinct small RNA pathway silences selfish genetic elements in the germline. Science 2006; 313: 320-324.
27. Takada S等. Mouse microRNA profiles determined with a new and sensitive cloning method. Nucleic Acids Res 2006; 34: e115.
Claims (16)
- ヒト上皮のサンプル中のヒト角化細胞の表皮分化の状態を決定するための方法であって、前記角化細胞中のhsa−miR−455−3p、hsa−miR−141、hsa−miR−148a、hsa−miR−182、hsa−miR−224、hsa−miR−26a、hsa−miR−26b、hsa−miR−361−5p、hsa−miR−425、hsa−miR−92b、hsa−let−7i、hsa−miR−22、hsa−miR−221、hsa−miR−222、hsa−miR−29a、hsa−miR−29b、hsa−miR−663、hsa−miR−30a及びhsa−miR−30cから選択される少なくとも1つのmiRNAの発現レベルを決定し、選択されたmiRNAの発現レベルを、好ましくは同一の株又は同一の集団から得る、培養下の未分化角化細胞又は分化表皮角化細胞中で選択されたmiRNAの発現の平均レベルと比較することを含む、方法。
- hsa−miR−455−3p、hsa−miR−141、hsa−miR−148a、hsa−miR−182、hsa−miR−224、hsa−miR−26a、hsa−miR−26b、hsa−miR−361−5p、hsa−miR−425及びhsa−miR−92bから選択される少なくとも1つのmiRNAの発現のレベルが、培養中の未分化角化細胞中の前記miRNAの発現の平均レベルよりも統計的に大きい場合、前記角化細胞は分化されたと考慮される、請求項1に記載の方法。
- hsa−let−7i、hsa−miR−22、hsa−miR−221、hsa−miR−222、hsa−miR−29a、hsa−miR−29b、hsa−miR−663、hsa−miR−30a及びhsa−miR−30cから選択される少なくとも1つのmiRNAの発現のレベルが、分化した表皮角化細胞中の前記miRNAの発現の平均レベルよりも統計的に大きい場合、前記角化細胞は未分化であると考慮される、請求項1に記載の方法。
- ヒト上皮のサンプル中に存在する表皮分化の差異を評価する方法であって、前記上皮の角化細胞の2層間で、hsa−miR−455−3p、hsa−miR−141、hsa−miR−148a、hsa−miR−182、hsa−miR−224、hsa−miR−26a、hsa−miR−26b、hsa−miR−361−5p、hsa−miR−425、hsa−miR−92b、hsa−let−7i、hsa−miR−22、hsa−miR−221、hsa−miR−222、hsa−miR−29a、hsa−miR−29b、hsa−miR−663、hsa−miR−30a及びhsa−miR−30cから選択される少なくとも1つのmiRNAの発現のレベルを比較することを含む、方法。
- 2層間の表皮分化の差異が、1.3よりも大きい因子で、一方の層におけるhsa−miR−455−3p、hsa−miR−141、hsa−miR−148a、hsa−miR−182、hsa−miR−224、hsa−miR−26a、hsa−miR−26b、hsa−miR−361−5p、hsa−miR−425及びhsa−miR−92bから選択される少なくとも1つのmiRNAの発現が他方よりも大きいことを特徴とする、請求項4に記載の方法。
- 2層間の表皮分化の差異が、1.3よりも大きい因子で、一方の層におけるhsa−let−7i、hsa−miR−22、hsa−miR−221、hsa−miR−222、hsa−miR−29a、hsa−miR−29b、hsa−miR−663、hsa−miR−30a及びhsa−miR−30cから選択される少なくとも1つのmiRNAの発現が他方よりも大きいことを特徴とする、請求項4に記載の方法。
- 前記サンプルを「再構築皮膚」型培養上皮から得る、請求項1から6の何れか一項に記載の方法。
- 上皮治療の効能を決定するための方法であって、治療の前後で、前記上皮の角化細胞中のhsa−miR−455−3p、hsa−miR−141、hsa−miR−148a、hsa−miR−182、hsa−miR−224、hsa−miR−26a、hsa−miR−26b、hsa−miR−361−5p、hsa−miR−425、hsa−miR−92b、hsa−let−7i、hsa−miR−22、hsa−miR−221、hsa−miR−222、hsa−miR−29a、hsa−miR−29b、hsa−miR−663、hsa−miR−30a及びhsa−miR−30cから選択される少なくとも1つの発現レベルを比較することを含む、方法。
- 前記治療が、放射線の適用によるか又は機械的効果の適用による、局所適用又は分子の注射からなる、請求項8に記載の方法。
- 上皮中の前記miRNAの少なくとも1つの発現レベルの修正を引き起こす場合、前記治療は効果的であると考慮される、請求項8又は請求項9に記載の方法。
- 上皮中の表皮分化プロセスのモジュレータをスクリーニングするための方法であって、スクリーニングするモジュレータの適用前後に、請求項1から3のいずれか一項に記載の方法を用いて、前記上皮中の角化細胞の表皮分化の状態を評価することを含む、方法。
- 前記モジュレータが、天然抽出物、複合体製剤、DNA分子、miRNA、siRNA、miRNA阻害剤、antagomir又は照射を用いた計測システムから得る化学成分である、請求項11に記載の方法。
- 上皮中の前記miRNAの少なくとも2つの発現レベルの修正を引き起こす場合、モジュレータが同定される、請求項11又は請求項12に記載の方法。
- 請求項4から7のいずれか一項に記載の方法を用いて、基底層と角質層の間の表皮中に存在する表皮分化の差異を決定し;
それを、基底層と角質層の間の同一の型の正常表皮に存在する表皮分化の平均差異と比較することを含む、表皮の状態を評価するための方法。 - 角化細胞の表皮分化の状態を決定するための、ヒト上皮サンプル中の角化細胞における、hsa−miR−455−3p、hsa−miR−141、hsa−miR−148a、hsa−miR−182、hsa−miR−224、hsa−miR−26a、hsa−miR−26b、hsa−miR−361−5p、hsa−miR−425、hsa−miR−92b、hsa−let−7i、hsa−miR−22、hsa−miR−221、hsa−miR−222、hsa−miR−29a、hsa−miR−29b、hsa−miR−663、hsa−miR−30a及びhsa−miR−30cから選択される少なくとも1つのmiRNAの発現アッセイの使用。
- hsa−miR−455−3p、hsa−miR−141、hsa−miR−148a、hsa−miR−182、hsa−miR−224、hsa−miR−26a、hsa−miR−26b、hsa−miR−361−5p、hsa−miR−425、hsa−miR−92b、hsa−let−7i、hsa−miR−22、hsa−miR−221、hsa−miR−222、hsa−miR−29a、hsa−miR−29b、hsa−miR−663、hsa−miR−30a及びhsa−miR−30cから選択される少なくとも1つのmiRNAの発現をアッセイするための手段と前記miRNAの発現の参照レベルを提供する情報を含む、ヒト角化細胞の分化の状態を決定するためのキット。
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EP2742148B1 (en) * | 2011-08-11 | 2017-06-28 | Hummingbird Diagnostics GmbH | Complex sets of mirnas as non-invasive biomarkers for psoriasis |
FR2987371B1 (fr) * | 2012-02-24 | 2016-01-01 | Isp Investments Inc | Methode d'identification in vitro de composes modulateurs de la differenciation cellulaire par dosage du micro-arn mir-203 |
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