CCN1是CCN家族六個成員之ㄧ，為分泌型的胞外間質蛋白，可藉由和不同的integrin接受器結合來調控細胞的附著、移動、增生、存活和分化。從小鼠胚胎天數第9.5天到出生前，可以偵測到CCN1 RNA被大量表現。利用標定基因的研究方法，可證明CCN1對於心血管系統發育極為重要。缺乏CCN1的胚胎會因為胎盤血管生成不全及血管構造的不健全造成胚胎死亡，而CCN1半量短少的小鼠會有心室心房中隔缺失的現象，與人類的心室心房中隔缺損的疾病相似。CCN1在胚胎後期的功能已有許多研究報導，然而，但對於早期胚胎發育，CCN1的表現如何目前尚未清楚。此外，在我們先前的結果發現，會有部份的胚胎體(Embryoid body)分化成跳動的心肌細胞且同時表現CCN1；當給予胚胎體純化的CCN1蛋白時，會有較高比例的胚胎體分化成跳動的心肌細胞。胚胎體是模擬早期的胚胎形成且表現CCN1，因此，想透過早期的胚胎發育去觀察CCN1的表現位置。所利用的CCN1+/-動物模式是將LacZ基因是先置入動物本身的CCN1基因前面，如此ㄧ來，當CCN1蛋白被表現時，可以利用X-gal染色法觀察到CCN1所表現的位置。透過CCN1+/-動物模式發現，CCN1最早於胚胎天數第7.5天開始表現於胚胎，主要表現於中胚層的發育，包括早期的心血管系統以及脊索，另外，圍成憩室的內胚層細胞也有表現CCN1，而胚外組織則可追朔至胚胎天數第6.5天。綜合所有觀察，在胚胎本身，CCN1最早在心臟開始的雛形即有表現，且此時期的心肌細胞尚未跳動，代表CCN1對於幹細胞發育成心肌細胞的過程可能扮演關鍵角色。
CCN1在成體幾乎不表現，然而當心臟受損後，CCN1會被大量表現，此外，FasL在過去的研究中證實會促使心肌細胞凋亡，因此，利用大鼠心肌H9c2細胞株當做實驗對象，進一步觀察心肌細胞凋亡路徑中，CCN1和FasL之間的關係。利用偵測活性氧分子(ROS)的試劑─DC-FDA，證實活性氧分子參與CCN1誘導心肌細胞凋亡的路徑中。此外，我們發現CCN1和FasL造成H9c2細胞凋亡具有協同作用，進一步證實，此協同作用現象不是透過增加細胞膜上的Fas量。我們的結果證實，CCN1和FasL會誘使H9c2協同的細胞凋亡現象發生，但其中的作用的機制需要更進一步去研究。

CCN1, a member of the CCN family, is an extracellular matrix-associated protein. The functions of CCN1 include cell adhesion, migration, proliferation, survival, and differentiation through binding to different integrin receptors. CCN1 RNA is highly expressed from embryonic day (E) 9.5 and declines after birth. CCN1 plays an important role in developing cardiovascular system, demonstrated by gene-targeting studies. CCN1-null mice suffered embryonic lethality due to insufficient placental vascularization and compromised vessel integrity. In addition, CCN1-deficient embryos display atrioventricular septal defects, reminiscent of AVSD in humans. The functions of CCN1 in late embryogenesis have been reported, but CCN1 expression is still not clear in early developing embryo. Furthermore, in in vitro embryoid body (EB) culture, CCN1 expression was specifically associated with differentiated beating cardiomyocytes, and greater proportion of EB cells differentiated into cardiomyocytes upon treatment with purified CCN1 protein. EB mimicked early embryonic forming and expressed CCN1, hence the CCN1 local expression could be fined through early embryogenesis. A lacZ gene was previously placed under the control of the endogenous CCN1 promoter in the Ccn1+/- mice. Hence, CCN1 expression in embryos can be reflected by the X-gal staining. CCN1 started to express as early as E7.5 in embryos. CCN1 expression was mainly in developing mesoderm, including cardiovascular system and notochord. CCN1 also displayed in embryonic endoderm forming foregut and hindgut. CCN1 in extraembryonic part could go back at E6.5. In conclusion, CCN1was firstly expressed when cardiac crescent just formed. The cardiomyocytes do not beat this stage, meaning that CCN1 may play a key role for stem cells differentiating to cardiomyocytes.
CCN1 expression subsides in adult, but the expression of CCN1 increases after heart injury. FasL has been shown to induce cardiomyocytes apoptosis. Using rat H9c2 cardiomyoblast cells, we further examined ant possible interaction between CCN1and FasL in cardiomycytes apoptosis. In our study, we proved that ROS (reactive oxygen species) was involved in CCN1-induced cardiomyocytes apoptosis by using DCF-DA ROS detection reagent. Besides, we found that CCN1 can synergize with FasL to induce H9c2 cells apoptosis. Furthermore, we showed that the synergistic effect of CCN1 and FasL cotreatment was not due to increased expression of Fas on cell membrane. However, the mechanism of CCN1 and FasL synergistic effect needs to be further examined. In conclusion, we proved that CCN1 synergized with FasL to induce apoptosis in H9c2 cells.

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