美國(guó)科研人員發(fā)現(xiàn)了一種可調(diào)節(jié)血管生長(zhǎng)的“開關(guān)”——微型核糖核酸分子miR－132,，并且找到了控制該“開關(guān)”的方法。這一研究成果有望對(duì)癌癥和心腦血管疾病的治療產(chǎn)生積極影響,。
這項(xiàng)研究由美國(guó)加州大學(xué)圣迭戈分校醫(yī)學(xué)院和密歇根大學(xué)癌癥中心的研究人員共同完成,。研究小組在英國(guó)《自然·醫(yī)學(xué)》雜志網(wǎng)絡(luò)版上報(bào)告說(shuō)，他們發(fā)現(xiàn)在正常血管形成或再生期間,，形成血管內(nèi)壁的內(nèi)皮細(xì)胞會(huì)暴露在一種具有“開關(guān)”功效的物質(zhì)環(huán)境中,，導(dǎo)致血管開始擴(kuò)張、生長(zhǎng),。通過(guò)分析,，研究人員確定這個(gè)“開關(guān)”就是微型核糖核酸分子miR－132。
負(fù)責(zé)此項(xiàng)研究的病理學(xué)家戴維·切雷什說(shuō),，血管與這個(gè)“開關(guān)”的關(guān)系好比是汽車與油門,、剎車片之間的關(guān)系。在腫瘤的血管里,，miR－132分子非常豐富,，它具有保障血管廣泛生長(zhǎng)的能力，結(jié)果造成病變部位的血管像油門轟響,、剎車失靈的汽車一樣在人體組織內(nèi)闖蕩,。
切雷什說(shuō)，根據(jù)這一原理，科研人員制作出了遏制miR－132分子的物質(zhì)和miR－132分子補(bǔ)充物,。在對(duì)患有癌癥和視網(wǎng)膜疾病的老鼠進(jìn)行實(shí)驗(yàn)時(shí),，研究者發(fā)現(xiàn)，遏制miR－132分子的物質(zhì)能使老鼠病變部位的血管生長(zhǎng)受到抑制,，阻止病情進(jìn)一步發(fā)展,。對(duì)于miR－132分子補(bǔ)充物的效果，研究者暫時(shí)沒(méi)有提供詳細(xì)資料,。
但他們認(rèn)為,，對(duì)于心腦血管疾病患者和因其他疾病血管受損者來(lái)說(shuō)，miR－132分子補(bǔ)充物可能有助于調(diào)節(jié)其血管生長(zhǎng),，緩解病情,。
目前，切雷什和同事正在設(shè)計(jì)一種納米粒,，以期將遏制miR－132分子的物質(zhì)和miR－132分子補(bǔ)充物準(zhǔn)確輸送到老鼠的病變部位,，并且降低這兩種物質(zhì)的毒副作用(高原)。（生物谷Bioon.com）
生物谷近期特別推薦會(huì)議：
2010細(xì)胞治療研究進(jìn)展與臨床前沿研討會(huì) www.Cell-therapies.net 2010年9月23日-25日天津召開
第一屆腫瘤基礎(chǔ)和轉(zhuǎn)化醫(yī)學(xué)國(guó)際研討會(huì) www.cancerasia.org 2010年10月12日-10月15日上海召開
生物谷推薦原文出處：
Nature Medicine doi:10.1038/nm.2186
MicroRNA-132–mediated loss of p120RasGAP activates the endothelium to facilitate pathological angiogenesis
Sudarshan Anand1, Bharat K Majeti1, Lisette M Acevedo1, Eric A Murphy1, Rajesh Mukthavaram1, Lea Scheppke1, Miller Huang1, David J Shields1, Jeffrey N Lindquist1, Philip E Lapinski2, Philip D King2, Sara M Weis1 & David A Cheresh1
Although it is well established that tumors initiate an angiogenic switch, the molecular basis of this process remains incompletely understood. Here we show that the miRNA miR-132 acts as an angiogenic switch by targeting p120RasGAP in the endothelium and thereby inducing neovascularization. We identified miR-132 as a highly upregulated miRNA in a human embryonic stem cell model of vasculogenesis and found that miR-132 was highly expressed in the endothelium of human tumors and hemangiomas but was undetectable in normal endothelium. Ectopic expression of miR-132 in endothelial cells in vitro increased their proliferation and tube-forming capacity, whereas intraocular injection of an antagomir targeting miR-132, anti–miR-132, reduced postnatal retinal vascular development in mice. Among the top-ranking predicted targets of miR-132 was p120RasGAP, which we found to be expressed in normal but not tumor endothelium. Endothelial expression of miR-132 suppressed p120RasGAP expression and increased Ras activity, whereas a miRNA-resistant version of p120RasGAP reversed the vascular response induced by miR-132. Notably, administration of anti–miR-132 inhibited angiogenesis in wild-type mice but not in mice with an inducible deletion of Rasa1 (encoding p120RasGAP). Finally, vessel-targeted nanoparticle delivery1 of anti–miR-132 restored p120RasGAP expression in the tumor endothelium, suppressed angiogenesis and decreased tumor burden in an orthotopic xenograft mouse model of human breast carcinoma. We conclude that miR-132 acts as an angiogenic switch by suppressing endothelial p120RasGAP expression, leading to Ras activation and the induction of neovascularization, whereas the application of anti–miR-132 inhibits neovascularization by maintaining vessels in the resting state.
