來自美國密歇根大學健康系統(tǒng)的研究人員研究了斑馬魚在遭受損傷后能夠再生受損視網(wǎng)膜的機制,，這一研究結(jié)果提示著有朝一日也能夠人類身上發(fā)揮同樣作用的新策略,，從而潛在性地允許醫(yī)生利用這些策略延緩或逆轉(zhuǎn)諸如視網(wǎng)膜黃斑變性和青光眼之類的疾病,。
基于以前的研究，密歇根大學分子和行為神經(jīng)科學研究所教授Daniel Goldman與博士后研究員Jin Wan和Rajesh Ramachandran一起利用模式動物斑馬魚開展研究,，發(fā)現(xiàn)肝素結(jié)合的類表皮生長因子(heparin binding epidermal growth factor-like growth factor, HB-EGF)在視網(wǎng)膜再生期間發(fā)揮著關(guān)鍵性作用,。這一研究發(fā)現(xiàn)于2012年2月14日發(fā)表在《細胞》子刊《發(fā)育細胞》期刊上。
Goldman說,，“我們發(fā)現(xiàn)這種因子足以激活整個過程,。”
當斑馬魚視網(wǎng)膜受損時，HB-EGF就得以表達并啟動一系列變化從而導致視網(wǎng)膜中已知為米勒神經(jīng)膠質(zhì)細胞(Müller glia)的某些細胞退回到干細胞狀態(tài),，然后這些處于干細胞狀態(tài)的細胞就能夠再生新的細胞從而修復(fù)損傷,。研究人員發(fā)現(xiàn)即便眼睛未受損時，HB-EGF也能促進米勒神經(jīng)膠質(zhì)細胞退回到干細胞狀態(tài),。
Goldman說,，下一步實驗就是探索這種因子及其相關(guān)途徑是否也能夠在哺乳動物中促進米勒神經(jīng)膠質(zhì)細胞去分化和形成干細胞。(生物谷：towersimper編譯)
doi:10.1016/j.devcel.2011.11.020
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HB-EGF Is Necessary and Sufficient for Müller Glia Dedifferentiation and Retina Regeneration
Jin Wan, Rajesh Ramachandran, Daniel Goldman
Müller glia (MG) dedifferentiation into a cycling population of multipotent progenitors is crucial to zebrafish retina regeneration. The mechanisms underlying MG dedifferentiation are unknown. Here we report that heparin-binding epidermal-like growth factor (HB-EGF) is rapidly induced in MG residing at the injury site and that pro-HB-EGF ectodomain shedding is necessary for retina regeneration. Remarkably, HB-EGF stimulates the formation of multipotent MG-derived progenitors in the uninjured retina. We show that HB-EGF mediates its effects via an EGFR/MAPK signal transduction cascade that regulates the expression of regeneration-associated genes, like ascl1a and pax6b. We also uncover an HB-EGF/Ascl1a/Notch/hb-egfa-signaling loop that helps define the zone of injury-responsive MG. Finally, we show that HB-EGF acts upstream of the Wnt/β-catenin-signaling cascade that controls progenitor proliferation. These data provide a link between extracellular signaling and regeneration-associated gene expression in the injured retina and suggest strategies for stimulating retina regeneration in mammals.
