JP2018168078A - Pdpn遺伝子又はタンパク質の発現促進剤、細胞遊走促進剤 - Google Patents
Pdpn遺伝子又はタンパク質の発現促進剤、細胞遊走促進剤 Download PDFInfo
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Abstract
Description
そこで、細胞遊走能の向上にあたっては、血行改善剤を用いて遊走促進因子を血中から補充することを試みたり、皮膚湿潤材を外用して細胞の遊走先である皮膚の湿潤状態を維持することにより血管からの浸出物を保持させるなどの対策が講じられている。さらに難治性の場合には、自己の血液を外用して遊走関連因子の補充を行う療法も行われている。しかし、従来の対策では、老化や疾患が原因で創傷治癒の遅延が生じている場合、そもそも自己血の細胞遊走促進機能が十分でないことがあり、また、人工的な増殖因子製剤の外用では、血液ほど多様な増殖因子を含有していないことで、十分な効果が得られないことがあった。したがって、線維芽細胞遊走促進に対する異なる手段の開発が望まれていた。
そこで、PDPNに起因する細胞遊走に関し、鋭意精鋭検討した結果、加齢によって細胞遊走能が低下した細胞であっても、PDPNの発現量を増加させる物質として見出したヒバマタエキスと共存させると、細胞遊走の促進に繋がることを確認し、本発明を完成させるに至った。
以下に示す遺伝子発現試験、細胞遊走試験において用いた被験物質は、市場に流通しているサガラメエキス(一丸ファルコス株式会社)、スサビノリエキス(一丸ファルコス株式会社)、ヒバマタエキス(丸善製薬株式会社)を使用した。
<加齢によるPDPN遺伝子発現量変化の確認時>
ヒト由来正常真皮線維芽細胞(28歳、63歳のヒトをドナーとする細胞)を、5.0×104cell/mLになるように10%FBSを含むD−MEM培地(Gibco、以下同じ。)に懸濁し、24ウェル細胞培養プレートに500μLずつ播種した。その後、37℃、5%CO2条件下で72時間培養後、線維芽細胞のTotal RNAを抽出した。
尚、ヒト由来正常真皮線維芽細胞(63歳のヒトをドナーとする細胞)群をコントロールとした。
<加齢により低下した細胞のPDPN遺伝子発現量を促進させる物質の探索時>
ヒト由来正常真皮線維芽細胞(63歳のヒトをドナーとする細胞)を、5.0×104cell/mLになるように10%FBSを含むD−MEM培地に懸濁し、24ウェル細胞培養プレート(True Line)に500μLずつ播種した。その後、37℃、5%CO2条件下で24時間培養後、被験物質を最終濃度100ppmとなるように、培地に添加した。37℃、5%CO2条件下でさらに72時間培養後、線維芽細胞のTotal RNAを抽出した。尚、被験物質非添加群をコントロールとした。
ヒト由来正常真皮線維芽細胞(28歳、63歳のヒトをドナーとする細胞)を、5.0×104cell/mLになるように10%FBSを含むD−MEM培地に懸濁し、12ウェル細胞培養プレートに1000μLずつ播種した。その後、37℃、5%CO2条件下で24時間培養した。24時間後、ヒバマタエキスを終濃度100ppm(原料の溶液分)になるように添加した。更に24時間後、培地を除去し、観察したい所定の細胞に対して、緑色の蛍光試薬(Calcein、CBI)又は赤色の蛍光試薬(Cell Explorer Live Cell Tracking KitのTrack It Red)を添加し、37℃、5%CO2下で30分間インキュベートすることで細胞を前調整した。30分間後、PBS(−)で洗浄し、7.5×105cell/mLとなるように10%FBSを含むD−MEM培地に分散し、Culture−Insert in μ−Dish 35mm, high (Wide of cell−free gap 500μm±50μm、ibidi社製)の左側の区画に赤色の蛍光試薬で染色した細胞を、右側の区画に緑色の蛍光試薬で染色した細胞を70μLずつ播種した。37℃、5% CO2下で4時間インキュベート後、Insertを外し10%FBSを含むD−MEM培地を2mL加え、40時間後蛍光顕微鏡(BZ−X700、KEYENCE、位相差10倍レンズ)を用いて、細胞遊走の様子を観察した。細胞遊走能は、隔離して配置した細胞群の内、赤色に染色した細胞群から、他方の細胞群で緑色に染色した細胞群の当初配置されたエリア内へ遊走してきた赤色の細胞の数をカウントすることで、評価した。
図3上段中央列の図は、左側の区画に老齢細胞を赤色に染めたものを播種し、右側の区画に老齢細胞を緑色に染めたものを播種して実験を行った旨のイメージ図(上段)、0時間における細胞遊走状態の写真(中段)、40時間後の細胞遊走状態の写真(下段)である。
図3上段の右列の図は、左側の区画に老齢細胞にヒバマタエキスを添加した後に赤色に染めたものを播種し、右側の区画に老齢細胞(ヒバマタエキス非添加)を緑色に染めたものを播種して実験を行った旨のイメージ図(上段)、0時間における細胞遊走状態の写真(中段)、40時間後の細胞遊走状態の写真(下段)である。
Claims (2)
- 褐藻類ヒバマタ科ヒバマタ属に属するヒバマタの抽出物を含有するPDPN遺伝子又はタンパク質の発現促進剤。
- 褐藻類ヒバマタ科ヒバマタ属に属するヒバマタの抽出物を含有する細胞遊走促進剤。
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BIOL. PHARM. BULL., 2000, 23(3), P.291-297, JPN6019043807, ISSN: 0004151583 * |
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