探討人類真皮微血管內皮細胞中MCPIP 調控血管新生機制

Abstract

血管新生是一個以原有血管為基礎，進而發展出新微血管並提供血流供應系統的生理過程，於生理和病理中都佔有重要角色，例如在胚胎發展中，要藉由血管新生作用增加血管網路，使發育中的組織或器官獲得足夠的營養和氧氣供應。人體終其一生都需以精密的血管新生調控來維持正常生理現象，血管新生的調控更影響許多組織病變與疾病，例如，心血管疾病、糖尿病、腫瘤生長，若無法正常調控，則會造成身體的損傷。先前的研究結果知道MCPIP是一種可以調控血管新生的核糖核酸酶，它可以通過透過誘導HIF1α和VEGF的上升促進血管生成 。然而，MCPIP的分子相互作用因子尚未闡明。我們的研究目的是探討MCPIP在人類真皮微血管內皮細胞-1（HMEC1）中的血管新生調節作用，本篇我們證明在VEGF的刺激下HMEC1中的MCPIP會隨著時間有不同表現量。此外，我們也發現將減少MCPIP基因的表現可以顯著的抑制血管生成。為了進一步闡明MCPIP在內皮細胞中的分子作用。我們通過蛋白質體學分析鑑定方式，找出幾種可能與MCPIP相互作用的蛋白質。本研究結果提供了MCPIP 亦可以被VEGF來調控而影響的血管生成並且探討可能調控的機制。我們的研究為MCPIP調節的血管生成提供了新的視角，並為VEGF所調控的血管新生路徑提供了新的研究方向。

Angiogenesis is a vital function in both physiology and pathology. The growth of blood vessels from existing vasculature could increase vascular networks which help the converged tissue or organ to get enough supply of nutrients and oxygen. Angiogenesis could also serve as an indicator which indicate the transition of tumor cells. Previous findings have demonstrated that MCPIP, a ribonuclease, which plays a key role in promoting angiogenesis via upregulating HIF1α and VEGF which leads to angiogenesis. However, the regulations and molecular interactors of MCPIP have not been elucidated. The aim of our study is to explore the potential regulation of MCPIP mediated angiogenesis in the human microvascular endothelial cells -1 (HMEC1). In our study, we have demonstrated that by establishing ex vivo angiogenesis assay using HMEC1 with VEGF treatment not only results in tubing formation but also MCPIP upregulation. In addition, we saw that specific inhibitory of MCPIP can reduce tube formation in ex vivo angiogenesis assay. To further clarify the molecular role of MCPIP in endothelial cells. We identify several candidate protein interactors of MCPIP through proteomic analysis. The results provide the potential possibility that MCPIP is one of the regulatory protein downstream of VEGF mediated angiogenesis pathways. Our data shed a new sight on MCPIP regulated angiogenesis and provides a conceivable visions of the potential biological regulations.