越來越多的證據(jù)表明，內(nèi)皮細胞并不簡單是提供氧氣和營養(yǎng)物的被動通道,。例如,，在胚胎生成過程中,，它們在循環(huán)系統(tǒng)形成之前誘導器官生成。
現(xiàn)在,，用一個70%肝切除的肝臟再生小鼠模型所進行的實驗,，顯示了內(nèi)皮細胞在切除手術(shù)后維持肝臟再生的一個分子通道。在所定義的肝臟內(nèi)皮細胞的一個亞組中VEGFR2的激發(fā),，導致內(nèi)皮特定轉(zhuǎn)錄因子Id1的上調(diào),，這種上調(diào)反過來又誘導Wnt2和肝細胞生長因子(HGF)的分泌，它又觸發(fā)肝細胞的增殖,。
這表明,，來自促進肝再生的脈管系統(tǒng)的誘導性信號，有可能被用來在這些手術(shù)之后啟動和加速肝臟恢復,。（生物谷Bioon.com）
生物谷推薦英文摘要：
Nature doi:10.1038/nature09493
Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration
Bi-Sen Ding,Daniel J. Nolan,Jason M. Butler,Daylon James,Alexander O. Babazadeh,Zev Rosenwaks,Vivek Mittal,Hideki Kobayashi,Koji Shido,David Lyden,Thomas N. Sato,Sina Y. Rabbany& Shahin Rafii
During embryogenesis, endothelial cells induce organogenesis before the development of circulation1, 2, 3, 4. These findings suggest that endothelial cells not only form passive conduits to deliver nutrients and oxygen, but also establish an instructive vascular niche, which through elaboration of paracrine trophogens stimulates organ regeneration, in a manner similar to endothelial-cell-derived angiocrine factors that support haematopoiesis5, 6, 7. However, the precise mechanism by which tissue-specific subsets of endothelial cells promote organogenesis in adults is unknown. Here we demonstrate that liver sinusoidal endothelial cells (LSECs) constitute a unique population of phenotypically and functionally defined VEGFR3+CD34?VEGFR2+VE-cadherin+FactorVIII+CD45? endothelial cells, which through the release of angiocrine trophogens initiate and sustain liver regeneration induced by 70% partial hepatectomy. After partial hepatectomy, residual liver vasculature remains intact without experiencing hypoxia or structural damage, which allows study of physiological liver regeneration. Using this model, we show that inducible genetic ablation of vascular endothelial growth factor (VEGF)-A receptor-2 (VEGFR2) in the LSECs impairs the initial burst of hepatocyte proliferation (days 1–3 after partial hepatectomy) and subsequent reconstitution of the hepatovascular mass (days 4–8 after partial hepatectomy) by inhibiting upregulation of the endothelial-cell-specific transcription factor Id1. Accordingly, Id1-deficient mice also manifest defects throughout liver regeneration, owing to diminished expression of LSEC-derived angiocrine factors, including hepatocyte growth factor (HGF) and Wnt2. Notably, in in vitro co-cultures, VEGFR2-Id1 activation in LSECs stimulates hepatocyte proliferation. Indeed, intrasplenic transplantation of Id1+/+ or Id1?/? LSECs transduced with Wnt2 and HGF (Id1?/?Wnt2+HGF+ LSECs) re-establishes an inductive vascular niche in the liver sinusoids of the Id1?/? mice, initiating and restoring hepatovascular regeneration. Therefore, in the early phases of physiological liver regeneration, VEGFR2-Id1-mediated inductive angiogenesis in LSECs through release of angiocrine factors Wnt2 and HGF provokes hepatic proliferation. Subsequently, VEGFR2-Id1-dependent proliferative angiogenesis reconstitutes liver mass. Therapeutic co-transplantation of inductive VEGFR2+Id1+Wnt2+HGF+ LSECs with hepatocytes provides an effective strategy to achieve durable liver regeneration.
